Myasthenia Gravis

Autoimmune MONDO:0009688 Pathograph 14 Show in embeddings browser Neuromuscular Disease Autoimmune Disease

Myasthenia gravis is an autoimmune disorder in which autoantibodies, most commonly against the acetylcholine receptor, target the postsynaptic neuromuscular junction. Antibody binding triggers receptor internalization and classical complement activation with membrane attack complex formation, destroying postsynaptic membrane and impairing neuromuscular transmission. The result is fatigable skeletal muscle weakness, and thymic hyperplasia or thymoma is frequently implicated as a site of autoimmunization.

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2
Mappings
1
Definitions
1
Inheritance
3
Pathophys.
38
Phenotypes
14
Pathograph
4
Genes
11
Medical Actions
5
Subtypes
5
Datasets
10
References
2
Deep Research
🔗

Mappings

MONDO
MONDO:0009688 myasthenia gravis
skos:exactMatch ORPHA:589 ORPHA:589: CONSISTENT
Orphanet lists MONDO:0009688 as an exact cross-reference for myasthenia gravis.
ICD-10-CM
ICD10CM:G70.0 Myasthenia gravis
skos:exactMatch ORPHA:589 ORPHA:589: CONSISTENT
Orphanet lists ICD-10 G70.0 as an exact cross-reference for myasthenia gravis.
📘

Definitions

1
Orphanet disease definition
Orphanet defines myasthenia gravis as a rare, clinically heterogeneous, autoimmune disorder of the neuromuscular junction characterized by fatigable weakness of voluntary muscles.
CASE_DEFINITION
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"Myasthenia gravis (MG) is a rare, clinically heterogeneous, autoimmune disorder of the neuromuscular junction characterized by fatigable weakness of voluntary muscles."
Orphanet's definition supports the autoimmune neuromuscular junction framing of this entry.
👪

Inheritance

1
Multigenic/multifactorial inheritance HP:0001426
Non-Mendelian inheritance
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"Multigenic/multifactorial"
Orphanet records multigenic/multifactorial inheritance for myasthenia gravis.
◆

Subtypes

5
AChR Antibody-Positive MG
Most common form (~85%), with antibodies against acetylcholine receptors.
Show evidence (1 reference)
PMID:38789789 SUPPORT Human Clinical
"In generalised MG this is seen in nearly 90% patients. Other antibodies include those against muscle specific tyrosine kinase (MuSK) and lipoprotein receptor related protein 4 (LRP4). "
The deep-research review supports AChR-antibody-positive disease as the dominant generalized MG subtype and places MuSK/LRP4 antibody subtypes in context.
MuSK Antibody-Positive MG
Antibodies against muscle-specific kinase, typically more severe bulbar symptoms.
Show evidence (2 references)
PMID:21674519 SUPPORT
"Eighty-five percent were female, with disease onset typically in the fourth decade. Ocular and/or bulbar symptoms were present at onset in 79% of those studied."
Large cohort study confirms MuSK-MG has prominent bulbar involvement and female predominance.
PMID:21674519 SUPPORT
"Eighty-five percent were MGFA class III or greater, and crisis occurred in 28%."
MuSK-MG tends to be more severe with higher rates of myasthenic crisis.
Seronegative MG
No detectable AChR or MuSK antibodies, may have LRP4 or other antibodies.
Show evidence (1 reference)
PMID:38789789 SUPPORT Human Clinical
"Other antibodies include those against muscle specific tyrosine kinase (MuSK) and lipoprotein receptor related protein 4 (LRP4). "
The review supports the curation note that patients negative for routine AChR/MuSK testing may have other antibody-defined MG biology, including LRP4.
Ocular MG
Disease limited to extraocular muscles, may progress to generalized form.
Thymoma-Associated MG
MG associated with thymic tumors, often more severe.
⚙

Pathophysiology

3
Autoantibody-Mediated NMJ Dysfunction
Autoantibodies (primarily anti-AChR) target the postsynaptic membrane at neuromuscular junctions. Antibodies cause receptor internalization, complement-mediated destruction, and functional blockade, reducing acetylcholine signaling efficiency.
Skeletal Muscle Cell CL:0000188 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Skeletal Muscle Cell, annotated with cell of skeletal muscle (CL:0000188). CL:0000188 is a cell type from the Cell Ontology.
Neuromuscular Transmission GO:0007274 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves Neuromuscular Transmission, annotated with neuromuscular synaptic transmission (GO:0007274). GO:0007274 is a biological process from the Gene Ontology.
Show evidence (2 references)
PMID:37869140 SUPPORT
"Myasthenia gravis is a prototypic neuroimmune disorder with autoantibodies targeting the acetylcholine receptor complex at the neuromuscular junction."
Confirms that autoantibodies targeting the AChR complex at the NMJ are central to myasthenia gravis pathophysiology.
PMID:29266249 SUPPORT
"Approximately 74-88% of patients with gMG have acetylcholine receptor (AChR) autoantibodies."
Documents the prevalence of AChR autoantibodies in generalized myasthenia gravis.
Complement Activation
Anti-AChR antibodies activate the classical complement pathway, leading to membrane attack complex formation and destruction of the postsynaptic membrane architecture.
Activation of Membrane Attack Complex GO:0001905 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Activation of Membrane Attack Complex (GO:0001905). GO:0001905 is a biological process from the Gene Ontology. ↑ INCREASED
Membrane Attack Complex GO:0005579 Gene Ontology (GO) Relation: this pathophysiological event involves this cellular component This pathophysiological event involves Membrane Attack Complex (GO:0005579). GO:0005579 is a cellular component from the Gene Ontology.
Show evidence (3 references)
PMID:29266249 SUPPORT
"activation and amplification of complement results in the formation of membrane attack complexes (MACs), lipophilic proteins that damage cell membranes."
Describes how complement activation leads to MAC formation and subsequent membrane damage.
PMID:29266249 SUPPORT Model Organism
"Studies in animals lacking specific complement proteins have confirmed that MAC formation is required to induce experimental autoimmune MG (EAMG) and NMJ damage."
Animal studies demonstrate that MAC formation is essential for NMJ damage in myasthenia gravis.
PMID:37869140 SUPPORT
"Acetylcholine receptor antibodies are present in the majority of patients and are of IgG1 and IgG3 subtypes which can activate the complement system. The complement involvement plays a major role in the neuromuscular junction damage"
Confirms that AChR antibodies (IgG1 and IgG3) activate complement, contributing to NMJ damage.
Thymic Abnormalities
Marked thymic pathology - follicular hyperplasia or thymoma - is present in most AChR-antibody-positive patients. The thymus may serve as the site of autoimmunization, containing the AChR autoantigen, AChR-specific T cells, and autoantibody-secreting plasma cells needed to initiate and sustain the autoimmune response.
Thymic Epithelial Cell CL:0002293 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Thymic Epithelial Cell, annotated with epithelial cell of thymus (CL:0002293). CL:0002293 is a cell type from the Cell Ontology.
Show evidence (2 references)
PMID:21922466 SUPPORT
"The thymus plays a major role in the pathogenesis of MG with anti-AChR antibodies: it shows marked pathologic alterations (hyperplastic or tumoral) in most AChR-positive patients and contains the elements required to initiate and sustain an autoimmune reaction (AChR autoantigen, AChR-specific T..."
Demonstrates that the thymus shows pathologic changes in most AChR-positive MG patients and contains all elements needed to initiate and sustain autoimmunity.
PMID:21922466 SUPPORT
"Myasthenia gravis (MG) is an autoimmune disorder caused, in most cases, by autoantibodies against components of the neuromuscular junction, frequently the acetylcholine receptor (AChR), and less often the muscle-specific kinase receptor."
Confirms the autoimmune nature of myasthenia gravis with autoantibodies targeting NMJ components.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Myasthenia Gravis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

38
Cardiovascular 1
Raynaud Phenomenon OCCASIONAL HP:0030880 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Raynaud phenomenon (HP:0030880). HP:0030880 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0030880 | Raynaud phenomenon | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies Raynaud phenomenon as Occasional (29-5%) in myasthenia gravis.
Digestive 1
Dysphagia FREQUENT HP:0002015 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dysphagia (HP:0002015). HP:0002015 is a phenotype from the Human Phenotype Ontology.
Difficulty swallowing, common in MuSK-positive MG
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0002015 | Dysphagia | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies dysphagia as Frequent (79-30%) in myasthenia gravis.
Ear 1
Hearing Impairment OCCASIONAL HP:0000365 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hearing impairment (HP:0000365). HP:0000365 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0000365 | Hearing impairment | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies hearing impairment as Occasional (29-5%) in myasthenia gravis.
Endocrine 1
Hyperthyroidism OCCASIONAL HP:0000836 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hyperthyroidism (HP:0000836). HP:0000836 is a phenotype from the Human Phenotype Ontology.
Autoimmune thyroid disease co-occurs with MG
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0000836 | Hyperthyroidism | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies hyperthyroidism as Occasional (29-5%) in myasthenia gravis.
Eye 2
Ptosis FREQUENT HP:0000508 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ptosis (HP:0000508). HP:0000508 is a phenotype from the Human Phenotype Ontology.
Often first symptom, asymmetric drooping eyelids
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0000508 | Ptosis | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies ptosis as Frequent (79-30%) in myasthenia gravis.
Diplopia FREQUENT HP:0000651 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Diplopia (HP:0000651). HP:0000651 is a phenotype from the Human Phenotype Ontology.
Double vision from extraocular muscle weakness
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0000651 | Diplopia | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies diplopia as Frequent (79-30%) in myasthenia gravis.
Genitourinary 1
Glycosuria OCCASIONAL HP:0003076 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Glycosuria (HP:0003076). HP:0003076 is a phenotype from the Human Phenotype Ontology.
Associated with autoimmune comorbidity
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0003076 | Glycosuria | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies glycosuria as Occasional (29-5%) in myasthenia gravis.
Head and Neck 1
Weakness of Facial Musculature FREQUENT HP:0030319 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Weakness of facial musculature (HP:0030319). HP:0030319 is a phenotype from the Human Phenotype Ontology.
Facial weakness contributing to expressionless facies
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0030319 | Weakness of facial musculature | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies weakness of facial musculature as Frequent (79-30%) in myasthenia gravis.
Limbs 1
Limb Muscle Weakness FREQUENT HP:0003690 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Limb muscle weakness (HP:0003690). HP:0003690 is a phenotype from the Human Phenotype Ontology.
Proximal limb weakness, difficulty with overhead activities
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0003690 | Limb muscle weakness | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies limb muscle weakness as Frequent (79-30%) in myasthenia gravis.
Musculoskeletal 2
Muscle Weakness VERY_FREQUENT HP:0001324 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Muscle Weakness (HP:0001324). HP:0001324 is a phenotype from the Human Phenotype Ontology.
Fatigable weakness, worse with exertion
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0001324 | Muscle weakness | Very frequent (99-80%)"
Orphanet's curated HPO frequency annotation classifies muscle weakness as Very frequent (99-80%) in myasthenia gravis.
Skeletal Muscle Atrophy FREQUENT HP:0003202 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Skeletal muscle atrophy (HP:0003202). HP:0003202 is a phenotype from the Human Phenotype Ontology.
Muscle wasting in chronic disease, particularly MuSK-MG
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0003202 | Skeletal muscle atrophy | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies skeletal muscle atrophy as Frequent (79-30%) in myasthenia gravis.
Nervous System 2
Dysarthria FREQUENT HP:0001260 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dysarthria (HP:0001260). HP:0001260 is a phenotype from the Human Phenotype Ontology.
Slurred or nasal speech
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0001260 | Dysarthria | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies dysarthria as Frequent (79-30%) in myasthenia gravis.
Paresthesia OCCASIONAL HP:0003401 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Paresthesia (HP:0003401). HP:0003401 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0003401 | Paresthesia | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies paresthesia as Occasional (29-5%) in myasthenia gravis.
Respiratory 2
Dyspnea FREQUENT HP:0002094 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dyspnea (HP:0002094). HP:0002094 is a phenotype from the Human Phenotype Ontology.
Breathing difficulty from respiratory muscle weakness
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0002094 | Dyspnea | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies dyspnea as Frequent (79-30%) in myasthenia gravis.
Respiratory Failure OCCASIONAL HP:0002878 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Respiratory failure (HP:0002878). HP:0002878 is a phenotype from the Human Phenotype Ontology.
Myasthenic crisis, life-threatening
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0002878 | Respiratory failure | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies respiratory failure as Occasional (29-5%) in myasthenia gravis.
Constitutional 1
Fatigue FREQUENT HP:0012378 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fatigue (HP:0012378). HP:0012378 is a phenotype from the Human Phenotype Ontology.
Generalized fatigue distinct from muscle-specific weakness
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0012378 | Fatigue | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies fatigue as Frequent (79-30%) in myasthenia gravis.
Other 22
Ophthalmoparesis FREQUENT HP:0000597 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ophthalmoparesis (HP:0000597). HP:0000597 is a phenotype from the Human Phenotype Ontology.
Weakness of extraocular muscles
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0000597 | Ophthalmoparesis | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies ophthalmoparesis as Frequent (79-30%) in myasthenia gravis.
Dysphonia FREQUENT HP:0001618 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dysphonia (HP:0001618). HP:0001618 is a phenotype from the Human Phenotype Ontology.
Voice changes from laryngeal muscle weakness
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0001618 | Dysphonia | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies dysphonia as Frequent (79-30%) in myasthenia gravis.
Bulbar Palsy FREQUENT HP:0001283 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Bulbar palsy (HP:0001283). HP:0001283 is a phenotype from the Human Phenotype Ontology.
Weakness of muscles innervated by cranial nerves
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0001283 | Bulbar palsy | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies bulbar palsy as Frequent (79-30%) in myasthenia gravis.
Fatigable Weakness of Skeletal Muscles FREQUENT HP:0030197 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fatigable weakness of skeletal muscles (HP:0030197). HP:0030197 is a phenotype from the Human Phenotype Ontology.
Weakness worsens with repetitive use
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0030197 | Fatigable weakness of skeletal muscles | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies fatigable weakness of skeletal muscles as Frequent (79-30%) in myasthenia gravis.
Difficulty Climbing Stairs FREQUENT HP:0003551 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Difficulty climbing stairs (HP:0003551). HP:0003551 is a phenotype from the Human Phenotype Ontology.
Proximal weakness manifesting as difficulty with stairs
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0003551 | Difficulty climbing stairs | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies difficulty climbing stairs as Frequent (79-30%) in myasthenia gravis.
Abnormal Thymus Morphology FREQUENT HP:0000777 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abnormal thymus morphology (HP:0000777). HP:0000777 is a phenotype from the Human Phenotype Ontology.
Thymic hyperplasia or thymoma
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0000777 | Abnormality of the thymus | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies abnormality of the thymus as Frequent (79-30%) in myasthenia gravis.
Thymus Hyperplasia FREQUENT HP:0010516 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Thymus hyperplasia (HP:0010516). HP:0010516 is a phenotype from the Human Phenotype Ontology.
Present in 65-75% of AChR-positive patients
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0010516 | Thymus hyperplasia | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies thymus hyperplasia as Frequent (79-30%) in myasthenia gravis.
Thymoma OCCASIONAL HP:0100522 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Thymoma (HP:0100522). HP:0100522 is a phenotype from the Human Phenotype Ontology.
Thymic tumor present in 10-15% of MG patients
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0100522 | Thymoma | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies thymoma as Occasional (29-5%) in myasthenia gravis.
Myositis FREQUENT HP:0100614 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Myositis (HP:0100614). HP:0100614 is a phenotype from the Human Phenotype Ontology.
Inflammatory myopathy can co-occur with MG
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0100614 | Myositis | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies myositis as Frequent (79-30%) in myasthenia gravis.
Tongue Atrophy OCCASIONAL HP:0012473 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Tongue atrophy (HP:0012473). HP:0012473 is a phenotype from the Human Phenotype Ontology.
Tongue wasting, particularly in MuSK-MG
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0012473 | Tongue atrophy | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies tongue atrophy as Occasional (29-5%) in myasthenia gravis.
Single Fiber EMG Abnormality FREQUENT HP:0030006 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Single fiber EMG abnormality (HP:0030006). HP:0030006 is a phenotype from the Human Phenotype Ontology.
Key electrodiagnostic finding, increased jitter
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0030006 | Single fiber EMG abnormality | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies single fiber EMG abnormality as Frequent (79-30%) in myasthenia gravis.
Acetylcholine Receptor Antibody Positivity FREQUENT Anti-neuromuscular Junction acetylcholine receptor antibody positivity HP:0030208 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Anti-neuromuscular Junction acetylcholine receptor antibody positivity (HP:0030208). HP:0030208 is a phenotype from the Human Phenotype Ontology.
Present in ~85% of generalized MG
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0030208 | Acetylcholine receptor antibody positivity | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies acetylcholine receptor antibody positivity as Frequent (79-30%) in myasthenia gravis.
Anti-MuSK Antibody Positivity FREQUENT Anti-muscle-specific tyrosine kinase antibody HP:0030210 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Anti-muscle-specific tyrosine kinase antibody (HP:0030210). HP:0030210 is a phenotype from the Human Phenotype Ontology.
Orphanet classifies as Frequent (79-30%); the ~5-10% figure reflects prevalence among all MG patients, whereas the Orphanet frequency reflects detection rate among those tested for MuSK antibodies
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0030210 | Muscle specific kinase antibody positivity | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies muscle specific kinase antibody positivity as Frequent (79-30%) in myasthenia gravis.
Anti-Lrp4 Antibody Positivity OCCASIONAL HP:5000046 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Anti-Lrp4 antibody positivity (HP:5000046). HP:5000046 is a phenotype from the Human Phenotype Ontology.
Present in some double-seronegative cases
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:5000046 | Anti-Lrp4 antibody positivity | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies anti-Lrp4 antibody positivity as Occasional (29-5%) in myasthenia gravis.
Anti-titin Antibody Positivity FREQUENT HP:5000038 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Anti-titin antibody positivity (HP:5000038). HP:5000038 is a phenotype from the Human Phenotype Ontology.
Associated with thymoma and late-onset MG
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:5000038 | Anti-titin antibody positivity | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies anti-titin antibody positivity as Frequent (79-30%) in myasthenia gravis.
Anti-ryanodine Receptor Antibody FREQUENT HP:5000047 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Anti-ryanodine receptor antibody (HP:5000047). HP:5000047 is a phenotype from the Human Phenotype Ontology.
Key marker for thymoma-associated MG
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:5000047 | Anti-ryanodine receptor antibody | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies anti-ryanodine receptor antibody as Frequent (79-30%) in myasthenia gravis.
Anti-Kv1.4 Antibody FREQUENT HP:5000048 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Anti-Kv1.4 antibody (HP:5000048). HP:5000048 is a phenotype from the Human Phenotype Ontology.
Associated with myasthenic crisis and cardiac involvement
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:5000048 | Anti-Kv1.4 antibody | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies anti-Kv1.4 antibody as Frequent (79-30%) in myasthenia gravis.
Anti-DCC Netrin 1 Receptor Antibody Positivity FREQUENT HP:6000881 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Anti-DCC netrin 1 receptor antibody positivity (HP:6000881). HP:6000881 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:6000881 | Anti-DCC netrin 1 receptor antibody positivity | Frequent (79-30%)"
Orphanet's curated HPO frequency annotation classifies anti-DCC netrin 1 receptor antibody positivity as Frequent (79-30%) in myasthenia gravis.
Hashimoto Thyroiditis OCCASIONAL HP:0000872 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Hashimoto thyroiditis (HP:0000872). HP:0000872 is a phenotype from the Human Phenotype Ontology.
Autoimmune thyroiditis co-occurs with MG
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0000872 | Hashimoto thyroiditis | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies Hashimoto thyroiditis as Occasional (29-5%) in myasthenia gravis.
Rheumatoid Arthritis OCCASIONAL HP:0001370 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Rheumatoid arthritis (HP:0001370). HP:0001370 is a phenotype from the Human Phenotype Ontology.
Autoimmune comorbidity
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0001370 | Rheumatoid arthritis | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies rheumatoid arthritis as Occasional (29-5%) in myasthenia gravis.
Systemic Lupus Erythematosus OCCASIONAL HP:0002725 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Systemic lupus erythematosus (HP:0002725). HP:0002725 is a phenotype from the Human Phenotype Ontology.
Autoimmune comorbidity
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0002725 | Systemic lupus erythematosus | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies systemic lupus erythematosus as Occasional (29-5%) in myasthenia gravis.
Primary Adrenal Insufficiency OCCASIONAL HP:0008207 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Primary adrenal insufficiency (HP:0008207). HP:0008207 is a phenotype from the Human Phenotype Ontology.
Autoimmune comorbidity
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"HP:0008207 | Primary adrenal insufficiency | Occasional (29-5%)"
Orphanet's curated HPO frequency annotation classifies primary adrenal insufficiency as Occasional (29-5%) in myasthenia gravis.
🧬

Genetic Associations

4
HLA-B8 (Risk Factor)
HLA-DR3 (Risk Factor)
Polygenic MG Susceptibility (GWAS)
Show evidence (2 references)
PMID:39537604 SUPPORT Human Clinical
"We identified 12 independent genome-wide significant hits (P < 5e−8) across 11 loci. "
The deep-research report highlighted this 2024 GWAS/meta-analysis; it supports adding an explicit polygenic susceptibility assertion rather than only older single-locus notes.
PMID:39537604 SUPPORT Human Clinical
"Subgroup analyses revealed two of these were associated with early-onset (at age <50) and four with late-onset MG (at age ≥ 50). "
The GWAS supports distinct genetic contributions by age at onset, matching the research synthesis emphasis on early- versus late-onset MG.
CHRNA1 (Risk Factor)
Gene: CHRNA1 hgnc:1955 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is CHRNA1 (hgnc:1955). hgnc:1955 is a gene from the HUGO Gene Nomenclature Committee.
🗃️

External Assertions

1
Orphanet myasthenia gravis record
Orphanet Structured disease record ORPHA:589
Orphanet structured record for myasthenia gravis, including curated cross-references to MONDO, ICD-10, ICD-11, OMIM, MeSH, MedDRA, and UMLS identifiers.
Show evidence (4 references)
ORPHA:589 SUPPORT Other
"MONDO:0009688 | Exact"
The Orphanet cross-reference table exactly maps ORPHA:589 to MONDO:0009688.
ORPHA:589 SUPPORT Other
"ICD-10:G70.0 | Exact"
The Orphanet cross-reference table exactly maps ORPHA:589 to ICD-10 G70.0.
ORPHA:589 SUPPORT Other
"ICD-11:8C60 | Exact"
The Orphanet cross-reference table exactly maps ORPHA:589 to ICD-11 8C60.
+ 1 more reference
💊

Medical Actions

11
Acetylcholinesterase Inhibitors
Action: acetylcholinesterase inhibitor therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is acetylcholinesterase inhibitor therapy, annotated with Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy NCIT:C15986
Agent: acetylcholinesterase inhibitor NCIT:C47792 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses acetylcholinesterase inhibitor (NCIT:C47792). NCIT:C47792 is a therapeutic agent from the NCI Thesaurus.
First-line symptomatic treatment (pyridostigmine).
Mechanism Target:
MODULATES Autoantibody-Mediated NMJ Dysfunction — Pyridostigmine inhibits acetylcholinesterase at the neuromuscular junction, prolonging ACh availability and partially compensating for the reduced AChR density caused by autoantibody-mediated receptor internalization and complement destruction.
Show evidence (2 references)
PMID:36184373 SUPPORT
"Patients reported a median effectiveness of 60, IQR 28-78 and net benefit of 65, IQR 45-84."
Large cross-sectional study demonstrates patient-reported effectiveness of pyridostigmine.
PMID:36184373 SUPPORT
"Of all patients currently using pyridostigmine, 91% reported side effects (vs. 55% in the control group)."
While effective, pyridostigmine has high rate of side effects including GI symptoms.
Corticosteroids
Action: corticosteroid agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is corticosteroid agent therapy, annotated with Systemic Corticosteroid Therapy (NCIT:C122080). NCIT:C122080 is a clinical intervention from the NCI Thesaurus. Ontology label: Systemic Corticosteroid Therapy NCIT:C122080
Prednisone for immunosuppression, mainstay of therapy.
Mechanism Target:
INHIBITS Autoantibody-Mediated NMJ Dysfunction — Corticosteroids suppress the autoimmune B and T cell responses that drive AChR autoantibody production, progressively reducing the antibody burden at the neuromuscular junction.
INHIBITS Thymic Abnormalities — Corticosteroids suppress thymic inflammation and lymphoproliferation, dampening the autoreactive T cell activation that originates in the thymus.
Thymectomy
Action: thymectomyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is thymectomy (NCIT:C29894). NCIT:C29894 is a clinical intervention from the NCI Thesaurus. Ontology label: Thymectomy NCIT:C29894
Surgical removal of thymus, improves outcomes in appropriate patients.
Mechanism Target:
INHIBITS Thymic Abnormalities — Thymectomy removes the hyperplastic or thymomatous thymus that harbors the autoreactive T cells and AChR-expressing myoid cells that initiate and sustain the AChR autoimmune response.
Show evidence (2 references)
PMID:27509100 SUPPORT
"Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001)"
Landmark randomized trial demonstrates thymectomy improves clinical outcomes in nonthymomatous MG.
PMID:27509100 SUPPORT
"Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001)."
Thymectomy reduces need for additional immunosuppression and hospitalizations.
Azathioprine
Action: immune suppressant agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is immune suppressant agent therapy, annotated with Immunosuppressive Therapy (NCIT:C15261). NCIT:C15261 is a clinical intervention from the NCI Thesaurus. Ontology label: Immunosuppressive Therapy NCIT:C15261
Steroid-sparing immunosuppressant.
Mechanism Target:
INHIBITS Autoantibody-Mediated NMJ Dysfunction — Azathioprine, a purine antimetabolite, suppresses lymphocyte proliferation, reducing autoreactive B and T cell populations and thereby lowering AChR autoantibody production at the neuromuscular junction.
Mycophenolate Mofetil
Action: immune suppressant agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is immune suppressant agent therapy, annotated with Immunosuppressive Therapy (NCIT:C15261). NCIT:C15261 is a clinical intervention from the NCI Thesaurus. Ontology label: Immunosuppressive Therapy NCIT:C15261
Alternative immunosuppressant.
Mechanism Target:
INHIBITS Autoantibody-Mediated NMJ Dysfunction — Mycophenolate mofetil inhibits inosine monophosphate dehydrogenase, selectively suppressing lymphocyte proliferation and reducing AChR autoantibody production.
Rituximab
Action: immune suppressant agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is immune suppressant agent therapy, annotated with Immunosuppressive Therapy (NCIT:C15261). NCIT:C15261 is a clinical intervention from the NCI Thesaurus. Ontology label: Immunosuppressive Therapy NCIT:C15261
Anti-CD20 antibody, effective in refractory cases.
Mechanism Target:
INHIBITS Autoantibody-Mediated NMJ Dysfunction — Rituximab depletes CD20+ B cells and plasmablasts, reducing the pool of antibody-secreting cells and lowering AChR (or MuSK) autoantibody titers that mediate NMJ dysfunction.
Eculizumab
Action: complement 5 inhibitor agent therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is complement 5 inhibitor agent therapy, annotated with Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy NCIT:C15986
Agent: complement inhibitor NCIT:C199456 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses complement inhibitor (NCIT:C199456). NCIT:C199456 is a therapeutic agent from the NCI Thesaurus.
Complement inhibitor (anti-C5), approved for refractory AChR+ MG.
Mechanism Target:
INHIBITS Complement Activation — Eculizumab is a monoclonal antibody that binds complement component C5, blocking cleavage to C5a and C5b and preventing membrane attack complex formation at the neuromuscular junction.
Show evidence (2 references)
PMID:29066163 SUPPORT
"Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis."
Phase 3 REGAIN trial evaluated eculizumab in refractory generalized MG.
PMID:29066163 SUPPORT
"Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group."
Eculizumab reduced exacerbation rates compared to placebo.
Plasma Exchange
Rapid removal of antibodies, used for myasthenic crisis.
Mechanism Target:
INHIBITS Autoantibody-Mediated NMJ Dysfunction — Plasma exchange physically removes circulating AChR and MuSK autoantibodies from the bloodstream, rapidly reducing the antibody burden at the neuromuscular junction.
Show evidence (1 reference)
PMID:21674519 SUPPORT
"Plasma exchange (PLEX) produced improvement in 93%, whereas only 61% improved after intravenous immunoglobulin."
Plasma exchange is highly effective, particularly in MuSK-MG where it outperforms IVIG.
Intravenous Immunoglobulin
Immunomodulation, used for exacerbations and crisis.
Mechanism Target:
INHIBITS Autoantibody-Mediated NMJ Dysfunction — IVIG modulates autoantibody activity via Fc receptor saturation and complement inhibition, reducing the effective titer of pathogenic AChR autoantibodies at the neuromuscular junction.
Efgartigimod
Action: FcRn antagonist therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is FcRn antagonist therapy, annotated with Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy NCIT:C15986
FcRn antagonist approved for generalized AChR-positive MG; reduces pathogenic IgG levels by blocking neonatal Fc receptor recycling.
Mechanism Target:
INHIBITS Autoantibody-Mediated NMJ Dysfunction — Efgartigimod blocks the neonatal Fc receptor (FcRn), preventing IgG recycling and accelerating catabolism of pathogenic AChR autoantibodies, thereby reducing the antibody burden at the neuromuscular junction.
Show evidence (2 references)
PMID:37602255 SUPPORT Human Clinical
"Efgartigimod is already approved for the treatment of generalized MG"
Review confirms FDA approval of efgartigimod for generalized MG.
PMID:37602255 SUPPORT Human Clinical
"FcRn receptors prevent the catabolism of IgG by impeding their lysosomal degradation and facilitating their extracellular release at physiological pH, consequently extending the IgG half-life. "
The research synthesis emphasized FcRn biology; this evidence links the treatment assertion to its mechanism of lowering pathogenic IgG.
Rozanolixizumab
Action: FcRn antagonist therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is FcRn antagonist therapy, annotated with Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. Ontology label: Pharmacotherapy NCIT:C15986
Subcutaneous FcRn antagonist for generalized myasthenia gravis in adults who are anti-AChR or anti-MuSK antibody positive; reduces pathogenic IgG via neonatal Fc receptor blockade.
Mechanism Target:
INHIBITS Autoantibody-Mediated NMJ Dysfunction — Rozanolixizumab blocks FcRn to accelerate IgG catabolism, reducing circulating AChR autoantibody levels and lessening antibody-mediated disruption of neuromuscular transmission.
Show evidence (3 references)
PMID:37059507 SUPPORT Human Clinical
"We enrolled patients (aged ≥18 years) with acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) autoantibody-positive generalised myasthenia gravis"
The registrational phase 3 trial enrolled both anti-AChR and anti-MuSK antibody-positive generalized MG, which is the population the treatment is indicated for.
PMID:37059507 SUPPORT Human Clinical
"Rozanolixizumab showed clinically meaningful improvements in patient-reported and investigator-assessed outcomes in patients with generalised myasthenia gravis, for both 7 mg/kg and 10 mg/kg doses."
Phase 3 efficacy result supporting rozanolixizumab as an active treatment for generalized MG.
PMID:37602255 SUPPORT Human Clinical
"rozanolixizumab is under review by health authorities"
Historical regulatory context only - this 2023 review predates approval; the drug has since been approved for generalized MG, so this quote no longer describes current status.
🌍

Environmental Factors

4
Infections
Infectious agent exposure ECTO:3000000 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is Infectious agent exposure, annotated with exposure to organism (ECTO:3000000). ECTO:3000000 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
May trigger or exacerbate disease, and is the single most common identified precipitant of myasthenic crisis. No specific pathogen has been established.
Show evidence (2 references)
PMID:9153452 SUPPORT Human Clinical
"Infection (usually pneumonia or upper respiratory infection) was the most common precipitating factor (38%), followed by no obvious cause (30%) and aspiration (10%)"
Retrospective review of 73 myasthenic crisis episodes over twelve years. Quantifies infection as the leading identified precipitant.
PMID:29372387 SUPPORT Human Clinical
"MG can be triggered and worsened by infections. No virus or other pathogen has been proven to have a specific link to MG"
Review supporting both halves of the note: infection as trigger and as exacerbant, together with the negative finding that no specific organism is established. The second sentence is the reason this entry is not narrowed to a named pathogen.
Medications
medication exposure ECTO:0000509 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is medication exposure, annotated with exposure to drug (ECTO:0000509). ECTO:0000509 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
Drugs that interfere with neuromuscular transmission may worsen disease. Fluoroquinolones are the best-evidenced example, including positive rechallenge.
Show evidence (2 references)
PMID:21879778 SUPPORT Human Clinical
"Six patients (16%) experienced a positive rechallenge, with recurrent myasthenia gravis exacerbation after fluoroquinolone reintroduction"
Analysis of 37 cases from the US FDA adverse event reporting system and the literature. Rechallenge is quoted in preference to the raw case count because recurrence on reintroduction is what distinguishes a drug effect from coincident deterioration in a relapsing disease.
PMID:29372387 SUPPORT Human Clinical
"Infections should be actively treated, but a few antibiotics are avoided due to potential interference with neuromuscular transmission"
Supports the general mechanism named in the note - interference with neuromuscular transmission - and the clinical practice of avoiding particular antibiotics. It does not name which agents, which is why the note does not either.
Stress
psychological stress XCO:0001265 Experimental Conditions Ontology (XCO) Relation: this environmental factor is this exposure This environmental factor is psychological stress, annotated with stress (XCO:0001265). XCO:0001265 is an exposure from the Experimental Conditions Ontology.
Physical or emotional stress can trigger exacerbations
Pregnancy
Variable effects on disease course, with the risk concentrated after delivery rather than during gestation.
Show evidence (1 reference)
PMID:42127347 SUPPORT Human Clinical
"During pregnancy, women were not more likely to be hospitalized for MG than in the prepregnancy year"
Population study of 112 women and 176 singleton pregnancies. The same abstract reports a roughly fivefold increase in prolonged MG admissions in the first three months postpartum, sustained across the first twelve months, so the variability the note describes is directional rather than random: gestation itself was not associated with more hospitalization, the postpartum period was.
🔬

Biochemical Markers

3
Anti-AChR Antibodies (Elevated)
Context: Present in ~85% of generalized MG
Anti-MuSK Antibodies (Elevated)
Context: Present in ~5-10% of MG, particularly seronegative cases
Anti-LRP4 Antibodies (Elevated)
Context: Present in some double-seronegative cases
📈

Progression

1
Onset
Age: All ages
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"Age of onset: All ages"
Orphanet records all ages as the age-of-onset category for myasthenia gravis.
📊

Prevalence

4
Europe (Orphanet annual incidence)
Annual Incidence 1.0–9.0 per 100,000 1–9 per 100,000
Orphanet reports a European annual incidence class of 1-9 per 100,000.
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"1-9 / 100 000 | Europe | Annual incidence | PMID:20130418,EXPERT"
The Orphanet epidemiology table provides a European annual incidence class for myasthenia gravis.
Europe (Orphanet point prevalence)
Point Prevalence 10.0–50.0 per 100,000 1–9 per 10,000
Orphanet reports a European point-prevalence class of 1-5 per 10,000.
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"1-5 / 10 000 | Europe | Point prevalence | PMID:17986328,EXPERT,PMID:2018"
The Orphanet epidemiology table provides a European point-prevalence class for myasthenia gravis.
Worldwide (Orphanet annual incidence)
Annual Incidence 0.1–0.9 per 100,000 1–9 per 1,000,000
Orphanet reports a worldwide annual incidence class of 1-9 per 1,000,000.
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"1-9 / 1 000 000 | Worldwide | Annual incidence | PMID:20565885"
The Orphanet epidemiology table provides a worldwide annual incidence class for myasthenia gravis.
Worldwide (Orphanet point prevalence)
Point Prevalence 1.0–9.0 per 100,000 1–9 per 100,000
Orphanet reports a worldwide point-prevalence class of 1-9 per 100,000.
Show evidence (1 reference)
ORPHA:589 SUPPORT Other
"1-9 / 100 000 | Worldwide | Point prevalence | PMID:20565885"
The Orphanet epidemiology table provides a worldwide point-prevalence class for myasthenia gravis.
📊

Related Datasets

5
Thymic B lineage cell landscape in Myasthenia gravis geo:GSE233180
Here, we provide a comprehensive and unbiased atlas of hematopoietic cell colonization in thymi derived from 12 immunotherapy-naïve patients with early-onset AChR-Ab+ MG (EOMG) using single-cell RNA sequencing (scRNA‑seq).
human SINGLE CELL RNA SEQ n=24
PMID:40117520
Identified by GEO DataSets index search for Myasthenia Gravis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Single-cell RNA-seq data of human PBMC from Myasthenia Gravis patients geo:GSE227835
Myasthenia Gravis (MG) is a chronic autoimmune disorder characterized by severe muscle weakness. However, the seronegative MG patient subgroup, which accounts for about 15% of MG patients, remains challenging diagnosis, and the immunopathology is understudied. Therefore, we performed single-cell RNA-sequencing analysis by peripheral blood and plasma proteome analysis for the seronegative MG patients. Numerical abnormalities were observed in multiple immune cells including B-cells compared to healthy controls (HC) and correlated with disease activities.
human SINGLE CELL RNA SEQ n=40
PMID:38711503
Identified by GEO DataSets index search for Myasthenia Gravis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Elevated N-linked glycosylation of IgG variable regions in myasthenia gravis disease subtypes geo:GSE182038
Elevated N-linked glycosylation of immunoglobulin G variable regions (IgG-VN-Glyc) is an emerging molecular phenotype associated with autoimmune disorders. To test the broader specificity of elevated IgG-VN-Glyc, we studied patients with distinct subtypes of myasthenia gravis (MG), a B cell-mediated autoimmune disease. Our experimental design included adaptive immune receptor repertoire sequencing to quantify and characterize N-glycosylation sites in the global B cell receptor repertoire, proteomics to examine glycosylation patterns of the circulating IgG, and production of human-derived recombinant autoantibodies, which were studied with mass spectrometry and antigen binding assays to confi...
human BULK RNA SEQ n=31
PMID:34544801
Identified by GEO DataSets index search for Myasthenia Gravis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Whole genome sequencing of 25 South African individuals with myasthenia gravis ega:EGAS00001003462
This study investigated the genetic basis of an ophthalmoplegic subphenotype of MG (OP-MG) which occurs in a proportion of myasthenics with juvenile symptom onset and African genetic ancestry. This OP-MG subphenotype is characterised by treatment resistant weakness of the extraocular muscles (EOMs) and the pathogenetic mechanism(s) underlying its development is unknown. The aim of this study was to use a hypothesis-generating genome-wide case-control analysis to identify candidate OP-MG susceptibility genes and pathways.
human
PMID:30881381
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Myasthenia Gravis"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
Genome-wide Association Study of Myasthenia Gravis dbgap:phs000726
The purpose of this project was to conduct a genome-wide associate study to search for the genetic factors that predispose to myasthenia gravis. The rationale for this study lies in the fact that, although the immunological and physiological processes affecting the neuromuscular junctions of myasthenia gravis patients are well understood, the spectrum of genetic factors that predispose to myasthenia gravis and influence its disease manifestations are not well known.
Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Myasthenia Gravis"). Retrieved 2026-08-02.
{ }

Source YAML

click to show 
name: Myasthenia Gravis
creation_date: '2025-12-19T01:12:52Z'
description: >-
  Myasthenia gravis is an autoimmune disorder in which autoantibodies, most commonly against the acetylcholine receptor, target the postsynaptic neuromuscular junction.
  Antibody binding triggers receptor internalization and classical complement activation with membrane attack complex formation, destroying postsynaptic membrane and impairing neuromuscular transmission.
  The result is fatigable skeletal muscle weakness, and thymic hyperplasia or thymoma is frequently implicated as a site of autoimmunization.
category: Autoimmune
parents:
- Neuromuscular Disease
- Autoimmune Disease
disease_term:
  preferred_term: myasthenia gravis
  term:
    id: MONDO:0009688
    label: myasthenia gravis
mappings:
  icd10cm_mappings:
  - term:
      id: ICD10CM:G70.0
      label: Myasthenia gravis
    mapping_predicate: skos:exactMatch
    mapping_source: ORPHA:589
    mapping_justification: Orphanet lists ICD-10 G70.0 as an exact cross-reference for myasthenia gravis.
    consistency:
    - reference: ORPHA:589
      consistent: CONSISTENT
      notes: "ICD-10:G70.0 | Exact"
  mondo_mappings:
  - term:
      id: MONDO:0009688
      label: myasthenia gravis
    mapping_predicate: skos:exactMatch
    mapping_source: ORPHA:589
    mapping_justification: Orphanet lists MONDO:0009688 as an exact cross-reference for myasthenia gravis.
    consistency:
    - reference: ORPHA:589
      consistent: CONSISTENT
      notes: "MONDO:0009688 | Exact"
definitions:
- name: Orphanet disease definition
  definition_type: CASE_DEFINITION
  description: >
    Orphanet defines myasthenia gravis as a rare, clinically heterogeneous,
    autoimmune disorder of the neuromuscular junction characterized by
    fatigable weakness of voluntary muscles.
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Myasthenia gravis (MG) is a rare, clinically heterogeneous, autoimmune disorder of the neuromuscular junction characterized by fatigable weakness of voluntary muscles."
    explanation: Orphanet's definition supports the autoimmune neuromuscular junction framing of this entry.
external_assertions:
- name: Orphanet myasthenia gravis record
  source: Orphanet
  assertion_type: Structured disease record
  external_id: ORPHA:589
  url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=589
  description: >
    Orphanet structured record for myasthenia gravis, including curated
    cross-references to MONDO, ICD-10, ICD-11, OMIM, MeSH, MedDRA, and UMLS
    identifiers.
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "MONDO:0009688 | Exact"
    explanation: The Orphanet cross-reference table exactly maps ORPHA:589 to MONDO:0009688.
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "ICD-10:G70.0 | Exact"
    explanation: The Orphanet cross-reference table exactly maps ORPHA:589 to ICD-10 G70.0.
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "ICD-11:8C60 | Exact"
    explanation: The Orphanet cross-reference table exactly maps ORPHA:589 to ICD-11 8C60.
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "UMLS:C0026896 | Exact"
    explanation: The Orphanet cross-reference table exactly maps ORPHA:589 to UMLS C0026896.
inheritance:
- name: Multigenic/multifactorial inheritance
  inheritance_term:
    preferred_term: Non-Mendelian inheritance
    term:
      id: HP:0001426
      label: Non-Mendelian inheritance
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Multigenic/multifactorial"
    explanation: Orphanet records multigenic/multifactorial inheritance for myasthenia gravis.
has_subtypes:
- name: AChR Antibody-Positive MG
  description: Most common form (~85%), with antibodies against acetylcholine receptors.
  evidence:
  - reference: PMID:38789789
    reference_title: Treating myasthenia gravis beyond the eye clinic
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      In generalised MG this is seen in nearly 90% patients. Other antibodies
      include those against muscle specific tyrosine kinase (MuSK) and
      lipoprotein receptor related protein 4 (LRP4).
    explanation: >
      The deep-research review supports AChR-antibody-positive disease as the
      dominant generalized MG subtype and places MuSK/LRP4 antibody subtypes in
      context.
- name: MuSK Antibody-Positive MG
  description: Antibodies against muscle-specific kinase, typically more severe bulbar symptoms.
  evidence:
  - reference: PMID:21674519
    reference_title: "Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts."
    supports: SUPPORT
    snippet: "Eighty-five percent were female, with disease onset typically in the fourth decade. Ocular and/or bulbar symptoms were present at onset in 79% of those studied."
    explanation: Large cohort study confirms MuSK-MG has prominent bulbar involvement and female predominance.
  - reference: PMID:21674519
    reference_title: "Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts."
    supports: SUPPORT
    snippet: "Eighty-five percent were MGFA class III or greater, and crisis occurred in 28%."
    explanation: MuSK-MG tends to be more severe with higher rates of myasthenic crisis.
- name: Seronegative MG
  description: No detectable AChR or MuSK antibodies, may have LRP4 or other antibodies.
  evidence:
  - reference: PMID:38789789
    reference_title: Treating myasthenia gravis beyond the eye clinic
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Other antibodies include those against muscle specific tyrosine kinase
      (MuSK) and lipoprotein receptor related protein 4 (LRP4).
    explanation: >
      The review supports the curation note that patients negative for routine
      AChR/MuSK testing may have other antibody-defined MG biology, including
      LRP4.
- name: Ocular MG
  description: Disease limited to extraocular muscles, may progress to generalized form.
- name: Thymoma-Associated MG
  description: MG associated with thymic tumors, often more severe.
prevalence:
- population: Europe (Orphanet annual incidence)
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_9_PER_100000
  rate_low: 1.0
  rate_high: 9.0
  percentage: 0.001-0.009
  notes: Orphanet reports a European annual incidence class of 1-9 per 100,000.
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "1-9 / 100 000 | Europe | Annual incidence | PMID:20130418,EXPERT"
    explanation: The Orphanet epidemiology table provides a European annual incidence class for myasthenia gravis.
- population: Europe (Orphanet point prevalence)
  measure_type: POINT_PREVALENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_low: 10.0
  rate_high: 50.0
  percentage: 0.01-0.05
  notes: Orphanet reports a European point-prevalence class of 1-5 per 10,000.
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "1-5 / 10 000 | Europe | Point prevalence | PMID:17986328,EXPERT,PMID:2018"
    explanation: The Orphanet epidemiology table provides a European point-prevalence class for myasthenia gravis.
- population: Worldwide (Orphanet annual incidence)
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_9_PER_1000000
  rate_low: 0.1
  rate_high: 0.9
  percentage: 0.0001-0.0009
  notes: Orphanet reports a worldwide annual incidence class of 1-9 per 1,000,000.
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "1-9 / 1 000 000 | Worldwide | Annual incidence | PMID:20565885"
    explanation: The Orphanet epidemiology table provides a worldwide annual incidence class for myasthenia gravis.
- population: Worldwide (Orphanet point prevalence)
  measure_type: POINT_PREVALENCE
  prevalence_class: BAND_1_9_PER_100000
  rate_low: 1.0
  rate_high: 9.0
  percentage: 0.001-0.009
  notes: Orphanet reports a worldwide point-prevalence class of 1-9 per 100,000.
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "1-9 / 100 000 | Worldwide | Point prevalence | PMID:20565885"
    explanation: The Orphanet epidemiology table provides a worldwide point-prevalence class for myasthenia gravis.
progression:
- phase: Onset
  age_range: All ages
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Age of onset: All ages"
    explanation: Orphanet records all ages as the age-of-onset category for myasthenia gravis.
pathophysiology:
- name: Autoantibody-Mediated NMJ Dysfunction
  description: >
    Autoantibodies (primarily anti-AChR) target the postsynaptic membrane at
    neuromuscular junctions. Antibodies cause receptor internalization,
    complement-mediated destruction, and functional blockade, reducing
    acetylcholine signaling efficiency.
  cell_types:
  - preferred_term: Skeletal Muscle Cell
    term:
      id: CL:0000188
      label: cell of skeletal muscle
  biological_processes:
  - preferred_term: Neuromuscular Transmission
    term:
      id: GO:0007274
      label: neuromuscular synaptic transmission
  evidence:
  - reference: PMID:37869140
    reference_title: "Role of complement in myasthenia gravis."
    supports: SUPPORT
    snippet: "Myasthenia gravis is a prototypic neuroimmune disorder with autoantibodies targeting the acetylcholine receptor complex at the neuromuscular junction."
    explanation: Confirms that autoantibodies targeting the AChR complex at the NMJ are central to myasthenia gravis pathophysiology.
  - reference: PMID:29266249
    reference_title: "Myasthenia gravis: the role of complement at the neuromuscular junction."
    supports: SUPPORT
    snippet: "Approximately 74-88% of patients with gMG have acetylcholine receptor (AChR) autoantibodies."
    explanation: Documents the prevalence of AChR autoantibodies in generalized myasthenia gravis.
- name: Complement Activation
  conforms_to: "complement_dysregulation#C5 Convertase Activation and Terminal Pathway Assembly"
  description: >
    Anti-AChR antibodies activate the classical complement pathway,
    leading to membrane attack complex formation and destruction of
    the postsynaptic membrane architecture.
  biological_processes:
  - preferred_term: Activation of Membrane Attack Complex
    term:
      id: GO:0001905
      label: activation of membrane attack complex
    modifier: INCREASED
  cellular_components:
  - preferred_term: Membrane Attack Complex
    term:
      id: GO:0005579
      label: membrane attack complex
  evidence:
  - reference: PMID:29266249
    reference_title: "Myasthenia gravis: the role of complement at the neuromuscular junction."
    supports: SUPPORT
    snippet: "activation and amplification of complement results in the formation of membrane attack complexes (MACs), lipophilic proteins that damage cell membranes."
    explanation: Describes how complement activation leads to MAC formation and subsequent membrane damage.
  - reference: PMID:29266249
    reference_title: "Myasthenia gravis: the role of complement at the neuromuscular junction."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Studies in animals lacking specific complement proteins have confirmed that MAC formation is required to induce experimental autoimmune MG (EAMG) and NMJ damage."
    explanation: Animal studies demonstrate that MAC formation is essential for NMJ damage in myasthenia gravis.
  - reference: PMID:37869140
    reference_title: "Role of complement in myasthenia gravis."
    supports: SUPPORT
    snippet: "Acetylcholine receptor antibodies are present in the majority of patients and are of IgG1 and IgG3 subtypes which can activate the complement system. The complement involvement plays a major role in the neuromuscular junction damage"
    explanation: Confirms that AChR antibodies (IgG1 and IgG3) activate complement, contributing to NMJ damage.
- name: Thymic Abnormalities
  description: >
    Marked thymic pathology - follicular hyperplasia or thymoma - is present
    in most AChR-antibody-positive patients. The thymus may serve as the site
    of autoimmunization, containing the AChR autoantigen, AChR-specific T
    cells, and autoantibody-secreting plasma cells needed to initiate and
    sustain the autoimmune response.
  notes: >
    Commonly quoted approximate frequencies (thymic hyperplasia in roughly
    two-thirds and thymoma in roughly 10-15% of AChR-positive patients) are
    not stated in the cited abstracts and are therefore kept out of the
    description; add them back only with a citable quantitative source.
  cell_types:
  - preferred_term: Thymic Epithelial Cell
    term:
      id: CL:0002293
      label: epithelial cell of thymus
  evidence:
  - reference: PMID:21922466
    reference_title: "The thymus in myasthenia gravis: Site of \"innate autoimmunity\"?"
    supports: SUPPORT
    snippet: "The thymus plays a major role in the pathogenesis of MG with anti-AChR antibodies: it shows marked pathologic alterations (hyperplastic or tumoral) in most AChR-positive patients and contains the elements required to initiate and sustain an autoimmune reaction (AChR autoantigen, AChR-specific T cells, and autoantibody-secreting plasma cells)."
    explanation: Demonstrates that the thymus shows pathologic changes in most AChR-positive MG patients and contains all elements needed to initiate and sustain autoimmunity.
  - reference: PMID:21922466
    reference_title: "The thymus in myasthenia gravis: Site of \"innate autoimmunity\"?"
    supports: SUPPORT
    snippet: "Myasthenia gravis (MG) is an autoimmune disorder caused, in most cases, by autoantibodies against components of the neuromuscular junction, frequently the acetylcholine receptor (AChR), and less often the muscle-specific kinase receptor."
    explanation: Confirms the autoimmune nature of myasthenia gravis with autoantibodies targeting NMJ components.
phenotypes:
- name: Muscle Weakness
  category: Neuromuscular
  frequency: VERY_FREQUENT
  diagnostic: true
  notes: Fatigable weakness, worse with exertion
  phenotype_term:
    preferred_term: Muscle Weakness
    term:
      id: HP:0001324
      label: Muscle weakness
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001324 | Muscle weakness | Very frequent (99-80%)"
    explanation: Orphanet's curated HPO frequency annotation classifies muscle weakness as Very frequent (99-80%) in myasthenia gravis.
- name: Ptosis
  category: Ocular
  frequency: FREQUENT
  diagnostic: true
  notes: Often first symptom, asymmetric drooping eyelids
  phenotype_term:
    preferred_term: Ptosis
    term:
      id: HP:0000508
      label: Ptosis
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000508 | Ptosis | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies ptosis as Frequent (79-30%) in myasthenia gravis.
- name: Diplopia
  category: Ocular
  frequency: FREQUENT
  notes: Double vision from extraocular muscle weakness
  phenotype_term:
    preferred_term: Diplopia
    term:
      id: HP:0000651
      label: Diplopia
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000651 | Diplopia | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies diplopia as Frequent (79-30%) in myasthenia gravis.
- name: Ophthalmoparesis
  category: Ocular
  frequency: FREQUENT
  notes: Weakness of extraocular muscles
  phenotype_term:
    preferred_term: Ophthalmoparesis
    term:
      id: HP:0000597
      label: Ophthalmoparesis
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000597 | Ophthalmoparesis | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies ophthalmoparesis as Frequent (79-30%) in myasthenia gravis.
- name: Dysphagia
  category: Bulbar
  frequency: FREQUENT
  notes: Difficulty swallowing, common in MuSK-positive MG
  phenotype_term:
    preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002015 | Dysphagia | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies dysphagia as Frequent (79-30%) in myasthenia gravis.
- name: Dysarthria
  category: Bulbar
  frequency: FREQUENT
  notes: Slurred or nasal speech
  phenotype_term:
    preferred_term: Dysarthria
    term:
      id: HP:0001260
      label: Dysarthria
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001260 | Dysarthria | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies dysarthria as Frequent (79-30%) in myasthenia gravis.
- name: Dysphonia
  category: Bulbar
  frequency: FREQUENT
  notes: Voice changes from laryngeal muscle weakness
  phenotype_term:
    preferred_term: Dysphonia
    term:
      id: HP:0001618
      label: Dysphonia
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001618 | Dysphonia | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies dysphonia as Frequent (79-30%) in myasthenia gravis.
- name: Bulbar Palsy
  category: Bulbar
  frequency: FREQUENT
  notes: Weakness of muscles innervated by cranial nerves
  phenotype_term:
    preferred_term: Bulbar palsy
    term:
      id: HP:0001283
      label: Bulbar palsy
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001283 | Bulbar palsy | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies bulbar palsy as Frequent (79-30%) in myasthenia gravis.
- name: Dyspnea
  category: Respiratory
  frequency: FREQUENT
  notes: Breathing difficulty from respiratory muscle weakness
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002094 | Dyspnea | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies dyspnea as Frequent (79-30%) in myasthenia gravis.
- name: Respiratory Failure
  category: Respiratory
  frequency: OCCASIONAL
  notes: Myasthenic crisis, life-threatening
  phenotype_term:
    preferred_term: Respiratory failure
    term:
      id: HP:0002878
      label: Respiratory failure
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002878 | Respiratory failure | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies respiratory failure as Occasional (29-5%) in myasthenia gravis.
- name: Fatigable Weakness of Skeletal Muscles
  category: Neuromuscular
  frequency: FREQUENT
  diagnostic: true
  notes: Weakness worsens with repetitive use
  phenotype_term:
    preferred_term: Fatigable weakness of skeletal muscles
    term:
      id: HP:0030197
      label: Fatigable weakness of skeletal muscles
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0030197 | Fatigable weakness of skeletal muscles | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies fatigable weakness of skeletal muscles as Frequent (79-30%) in myasthenia gravis.
- name: Limb Muscle Weakness
  category: Neuromuscular
  frequency: FREQUENT
  notes: Proximal limb weakness, difficulty with overhead activities
  phenotype_term:
    preferred_term: Limb muscle weakness
    term:
      id: HP:0003690
      label: Limb muscle weakness
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003690 | Limb muscle weakness | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies limb muscle weakness as Frequent (79-30%) in myasthenia gravis.
- name: Weakness of Facial Musculature
  category: Neuromuscular
  frequency: FREQUENT
  notes: Facial weakness contributing to expressionless facies
  phenotype_term:
    preferred_term: Weakness of facial musculature
    term:
      id: HP:0030319
      label: Weakness of facial musculature
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0030319 | Weakness of facial musculature | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies weakness of facial musculature as Frequent (79-30%) in myasthenia gravis.
- name: Difficulty Climbing Stairs
  category: Neuromuscular
  frequency: FREQUENT
  notes: Proximal weakness manifesting as difficulty with stairs
  phenotype_term:
    preferred_term: Difficulty climbing stairs
    term:
      id: HP:0003551
      label: Difficulty climbing stairs
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003551 | Difficulty climbing stairs | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies difficulty climbing stairs as Frequent (79-30%) in myasthenia gravis.
- name: Skeletal Muscle Atrophy
  category: Neuromuscular
  frequency: FREQUENT
  notes: Muscle wasting in chronic disease, particularly MuSK-MG
  phenotype_term:
    preferred_term: Skeletal muscle atrophy
    term:
      id: HP:0003202
      label: Skeletal muscle atrophy
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003202 | Skeletal muscle atrophy | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies skeletal muscle atrophy as Frequent (79-30%) in myasthenia gravis.
- name: Fatigue
  category: Neuromuscular
  frequency: FREQUENT
  notes: Generalized fatigue distinct from muscle-specific weakness
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0012378 | Fatigue | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies fatigue as Frequent (79-30%) in myasthenia gravis.
- name: Abnormal Thymus Morphology
  category: Immunological
  frequency: FREQUENT
  notes: Thymic hyperplasia or thymoma
  phenotype_term:
    preferred_term: Abnormal thymus morphology
    term:
      id: HP:0000777
      label: Abnormal thymus morphology
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000777 | Abnormality of the thymus | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies abnormality of the thymus as Frequent (79-30%) in myasthenia gravis.
- name: Thymus Hyperplasia
  category: Immunological
  frequency: FREQUENT
  notes: Present in 65-75% of AChR-positive patients
  phenotype_term:
    preferred_term: Thymus hyperplasia
    term:
      id: HP:0010516
      label: Thymus hyperplasia
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0010516 | Thymus hyperplasia | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies thymus hyperplasia as Frequent (79-30%) in myasthenia gravis.
- name: Thymoma
  category: Immunological
  frequency: OCCASIONAL
  notes: Thymic tumor present in 10-15% of MG patients
  phenotype_term:
    preferred_term: Thymoma
    term:
      id: HP:0100522
      label: Thymoma
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0100522 | Thymoma | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies thymoma as Occasional (29-5%) in myasthenia gravis.
- name: Myositis
  category: Neuromuscular
  frequency: FREQUENT
  notes: Inflammatory myopathy can co-occur with MG
  phenotype_term:
    preferred_term: Myositis
    term:
      id: HP:0100614
      label: Myositis
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0100614 | Myositis | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies myositis as Frequent (79-30%) in myasthenia gravis.
- name: Tongue Atrophy
  category: Bulbar
  frequency: OCCASIONAL
  notes: Tongue wasting, particularly in MuSK-MG
  phenotype_term:
    preferred_term: Tongue atrophy
    term:
      id: HP:0012473
      label: Tongue atrophy
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0012473 | Tongue atrophy | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies tongue atrophy as Occasional (29-5%) in myasthenia gravis.
- name: Single Fiber EMG Abnormality
  category: Diagnostic
  frequency: FREQUENT
  diagnostic: true
  notes: Key electrodiagnostic finding, increased jitter
  phenotype_term:
    preferred_term: Single fiber EMG abnormality
    term:
      id: HP:0030006
      label: Single fiber EMG abnormality
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0030006 | Single fiber EMG abnormality | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies single fiber EMG abnormality as Frequent (79-30%) in myasthenia gravis.
- name: Acetylcholine Receptor Antibody Positivity
  category: Immunological
  frequency: FREQUENT
  diagnostic: true
  notes: Present in ~85% of generalized MG
  phenotype_term:
    preferred_term: Anti-neuromuscular Junction acetylcholine receptor antibody positivity
    term:
      id: HP:0030208
      label: Anti-neuromuscular Junction acetylcholine receptor antibody positivity
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0030208 | Acetylcholine receptor antibody positivity | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies acetylcholine receptor antibody positivity as Frequent (79-30%) in myasthenia gravis.
- name: Anti-MuSK Antibody Positivity
  category: Immunological
  frequency: FREQUENT
  notes: Orphanet classifies as Frequent (79-30%); the ~5-10% figure reflects prevalence among all MG patients, whereas the Orphanet frequency reflects detection rate among those tested for MuSK antibodies
  phenotype_term:
    preferred_term: Anti-muscle-specific tyrosine kinase antibody
    term:
      id: HP:0030210
      label: Anti-muscle-specific tyrosine kinase antibody
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0030210 | Muscle specific kinase antibody positivity | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies muscle specific kinase antibody positivity as Frequent (79-30%) in myasthenia gravis.
- name: Anti-Lrp4 Antibody Positivity
  category: Immunological
  frequency: OCCASIONAL
  notes: Present in some double-seronegative cases
  phenotype_term:
    preferred_term: Anti-Lrp4 antibody positivity
    term:
      id: HP:5000046
      label: Anti-Lrp4 antibody positivity
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:5000046 | Anti-Lrp4 antibody positivity | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies anti-Lrp4 antibody positivity as Occasional (29-5%) in myasthenia gravis.
- name: Anti-titin Antibody Positivity
  category: Immunological
  frequency: FREQUENT
  notes: Associated with thymoma and late-onset MG
  phenotype_term:
    preferred_term: Anti-titin antibody positivity
    term:
      id: HP:5000038
      label: Anti-titin antibody positivity
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:5000038 | Anti-titin antibody positivity | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies anti-titin antibody positivity as Frequent (79-30%) in myasthenia gravis.
- name: Anti-ryanodine Receptor Antibody
  category: Immunological
  frequency: FREQUENT
  notes: Key marker for thymoma-associated MG
  phenotype_term:
    preferred_term: Anti-ryanodine receptor antibody
    term:
      id: HP:5000047
      label: Anti-ryanodine receptor antibody
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:5000047 | Anti-ryanodine receptor antibody | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies anti-ryanodine receptor antibody as Frequent (79-30%) in myasthenia gravis.
- name: Anti-Kv1.4 Antibody
  category: Immunological
  frequency: FREQUENT
  notes: Associated with myasthenic crisis and cardiac involvement
  phenotype_term:
    preferred_term: Anti-Kv1.4 antibody
    term:
      id: HP:5000048
      label: Anti-Kv1.4 antibody
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:5000048 | Anti-Kv1.4 antibody | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies anti-Kv1.4 antibody as Frequent (79-30%) in myasthenia gravis.
- name: Anti-DCC Netrin 1 Receptor Antibody Positivity
  category: Immunological
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Anti-DCC netrin 1 receptor antibody positivity
    term:
      id: HP:6000881
      label: Anti-DCC netrin 1 receptor antibody positivity
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:6000881 | Anti-DCC netrin 1 receptor antibody positivity | Frequent (79-30%)"
    explanation: Orphanet's curated HPO frequency annotation classifies anti-DCC netrin 1 receptor antibody positivity as Frequent (79-30%) in myasthenia gravis.
- name: Hyperthyroidism
  category: Autoimmune Comorbidity
  frequency: OCCASIONAL
  notes: Autoimmune thyroid disease co-occurs with MG
  phenotype_term:
    preferred_term: Hyperthyroidism
    term:
      id: HP:0000836
      label: Hyperthyroidism
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000836 | Hyperthyroidism | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies hyperthyroidism as Occasional (29-5%) in myasthenia gravis.
- name: Hashimoto Thyroiditis
  category: Autoimmune Comorbidity
  frequency: OCCASIONAL
  notes: Autoimmune thyroiditis co-occurs with MG
  phenotype_term:
    preferred_term: Hashimoto thyroiditis
    term:
      id: HP:0000872
      label: Hashimoto thyroiditis
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000872 | Hashimoto thyroiditis | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies Hashimoto thyroiditis as Occasional (29-5%) in myasthenia gravis.
- name: Rheumatoid Arthritis
  category: Autoimmune Comorbidity
  frequency: OCCASIONAL
  notes: Autoimmune comorbidity
  phenotype_term:
    preferred_term: Rheumatoid arthritis
    term:
      id: HP:0001370
      label: Rheumatoid arthritis
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001370 | Rheumatoid arthritis | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies rheumatoid arthritis as Occasional (29-5%) in myasthenia gravis.
- name: Systemic Lupus Erythematosus
  category: Autoimmune Comorbidity
  frequency: OCCASIONAL
  notes: Autoimmune comorbidity
  phenotype_term:
    preferred_term: Systemic lupus erythematosus
    term:
      id: HP:0002725
      label: Systemic lupus erythematosus
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002725 | Systemic lupus erythematosus | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies systemic lupus erythematosus as Occasional (29-5%) in myasthenia gravis.
- name: Raynaud Phenomenon
  category: Autoimmune Comorbidity
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Raynaud phenomenon
    term:
      id: HP:0030880
      label: Raynaud phenomenon
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0030880 | Raynaud phenomenon | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies Raynaud phenomenon as Occasional (29-5%) in myasthenia gravis.
- name: Paresthesia
  category: Neurological
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Paresthesia
    term:
      id: HP:0003401
      label: Paresthesia
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003401 | Paresthesia | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies paresthesia as Occasional (29-5%) in myasthenia gravis.
- name: Hearing Impairment
  category: Neurological
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Hearing impairment
    term:
      id: HP:0000365
      label: Hearing impairment
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000365 | Hearing impairment | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies hearing impairment as Occasional (29-5%) in myasthenia gravis.
- name: Glycosuria
  category: Metabolic
  frequency: OCCASIONAL
  notes: Associated with autoimmune comorbidity
  phenotype_term:
    preferred_term: Glycosuria
    term:
      id: HP:0003076
      label: Glycosuria
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003076 | Glycosuria | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies glycosuria as Occasional (29-5%) in myasthenia gravis.
- name: Primary Adrenal Insufficiency
  category: Endocrine
  frequency: OCCASIONAL
  notes: Autoimmune comorbidity
  phenotype_term:
    preferred_term: Primary adrenal insufficiency
    term:
      id: HP:0008207
      label: Primary adrenal insufficiency
  evidence:
  - reference: ORPHA:589
    reference_title: "Myasthenia gravis"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0008207 | Primary adrenal insufficiency | Occasional (29-5%)"
    explanation: Orphanet's curated HPO frequency annotation classifies primary adrenal insufficiency as Occasional (29-5%) in myasthenia gravis.
biochemical:
- name: Anti-AChR Antibodies
  presence: Elevated
  context: Present in ~85% of generalized MG
- name: Anti-MuSK Antibodies
  presence: Elevated
  context: Present in ~5-10% of MG, particularly seronegative cases
- name: Anti-LRP4 Antibodies
  presence: Elevated
  context: Present in some double-seronegative cases
genetic:
- name: HLA-B8
  association: Risk Factor
  notes: Associated with early-onset MG
- name: HLA-DR3
  association: Risk Factor
  notes: Associated with early-onset MG and thymic hyperplasia
- name: Polygenic MG Susceptibility
  association: GWAS
  notes: >
    Recent genome-wide meta-analysis supports a polygenic architecture with
    age-of-onset-specific HLA effects and multiple genome-wide significant loci.
  evidence:
  - reference: PMID:39537604
    reference_title: Genome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      We identified 12 independent genome-wide significant hits (P < 5e−8)
      across 11 loci.
    explanation: >
      The deep-research report highlighted this 2024 GWAS/meta-analysis; it
      supports adding an explicit polygenic susceptibility assertion rather than
      only older single-locus notes.
  - reference: PMID:39537604
    reference_title: Genome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Subgroup analyses revealed two of these were associated with early-onset
      (at age <50) and four with late-onset MG (at age ≥ 50).
    explanation: >
      The GWAS supports distinct genetic contributions by age at onset, matching
      the research synthesis emphasis on early- versus late-onset MG.
- name: CHRNA1
  gene_term:
    preferred_term: CHRNA1
    term:
      id: hgnc:1955
      label: CHRNA1
  association: Risk Factor
  notes: Acetylcholine receptor alpha subunit, rare variants
environmental:
- name: Infections
  exposure_term:
    preferred_term: Infectious agent exposure
    term:
      id: ECTO:3000000
      label: exposure to organism
  notes: May trigger or exacerbate disease, and is the single most common identified
    precipitant of myasthenic crisis. No specific pathogen has been established.
  evidence:
  - reference: PMID:9153452
    reference_title: "Myasthenic crisis: clinical features, mortality, complications, and risk factors for prolonged intubation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Infection (usually pneumonia or upper respiratory infection) was the most common precipitating factor (38%), followed by no obvious cause (30%) and aspiration (10%)"
    explanation: "Retrospective review of 73 myasthenic crisis episodes over twelve years. Quantifies infection as the leading identified precipitant."
  - reference: PMID:29372387
    reference_title: "Myasthenia gravis and infectious disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "MG can be triggered and worsened by infections. No virus or other pathogen has been proven to have a specific link to MG"
    explanation: "Review supporting both halves of the note: infection as trigger and as exacerbant, together with the negative finding that no specific organism is established. The second sentence is the reason this entry is not narrowed to a named pathogen."
- name: Medications
  exposure_term:
    preferred_term: medication exposure
    term:
      id: ECTO:0000509
      label: exposure to drug
  notes: Drugs that interfere with neuromuscular transmission may worsen disease.
    Fluoroquinolones are the best-evidenced example, including positive rechallenge.
  review_notes: The prior note named aminoglycosides and beta-blockers. Both are
    long-standing clinical convention and appear on avoid-lists, but no source was
    found whose abstract states either association directly, so the note now leads
    with the agent class that is evidenced rather than asserting an unsourced drug
    list. Aminoglycosides and beta-blockers should be reinstated by name if and when
    a citable source is found; their omission here is an evidence gap, not a
    judgement that the association is wrong.
  evidence:
  - reference: PMID:21879778
    reference_title: "Fluoroquinolone-associated myasthenia gravis exacerbation: evaluation of postmarketing reports from the US FDA adverse event reporting system and a literature review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Six patients (16%) experienced a positive rechallenge, with recurrent myasthenia gravis exacerbation after fluoroquinolone reintroduction"
    explanation: "Analysis of 37 cases from the US FDA adverse event reporting system and the literature. Rechallenge is quoted in preference to the raw case count because recurrence on reintroduction is what distinguishes a drug effect from coincident deterioration in a relapsing disease."
  - reference: PMID:29372387
    reference_title: "Myasthenia gravis and infectious disease."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Infections should be actively treated, but a few antibiotics are avoided due to potential interference with neuromuscular transmission"
    explanation: "Supports the general mechanism named in the note - interference with neuromuscular transmission - and the clinical practice of avoiding particular antibiotics. It does not name which agents, which is why the note does not either."
- name: Stress
  exposure_term:
    preferred_term: psychological stress
    term:
      id: XCO:0001265
      label: stress
  notes: Physical or emotional stress can trigger exacerbations
  review_notes: Left deliberately uncited. Targeted PubMed searches (stress
    precipitating myasthenic exacerbation; psychological stress and myasthenia
    gravis onset; patient-reported trigger factors) returned no study whose
    abstract states this claim directly. Note that the largest crisis-precipitant
    series cited on the Infections entry records no obvious cause in 30 percent of
    episodes rather than attributing them to stress. Per the evidence SOP the claim
    is kept as a note rather than attached to an approximately-relevant citation.
- name: Pregnancy
  notes: Variable effects on disease course, with the risk concentrated after
    delivery rather than during gestation.
  review_notes: Left without an exposure_term. ECTO was searched and carries no
    pregnancy exposure class; the near matches are CHEBI chemical terms, which would
    not validate against the exposure-term enum. Per the term-curation rule that no
    term beats a bad one, this stays unbound rather than being forced onto an
    approximate class.
  evidence:
  - reference: PMID:42127347
    reference_title: "Risk of Myasthenia Gravis Exacerbation During Pregnancy and Postpartum: A Nationwide Cohort Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "During pregnancy, women were not more likely to be hospitalized for MG than in the prepregnancy year"
    explanation: "Population study of 112 women and 176 singleton pregnancies. The same abstract reports a roughly fivefold increase in prolonged MG admissions in the first three months postpartum, sustained across the first twelve months, so the variability the note describes is directional rather than random: gestation itself was not associated with more hospitalization, the postpartum period was."
treatments:
- name: Acetylcholinesterase Inhibitors
  description: First-line symptomatic treatment (pyridostigmine).
  treatment_term:
    preferred_term: acetylcholinesterase inhibitor therapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: acetylcholinesterase inhibitor
      term:
        id: NCIT:C47792
        label: Acetylcholinesterase Inhibitor
  evidence:
  - reference: PMID:36184373
    reference_title: "The effectiveness and side effects of pyridostigmine in the treatment of myasthenia gravis: a cross-sectional study."
    supports: SUPPORT
    snippet: "Patients reported a median effectiveness of 60, IQR 28-78 and net benefit of 65, IQR 45-84."
    explanation: Large cross-sectional study demonstrates patient-reported effectiveness of pyridostigmine.
  - reference: PMID:36184373
    reference_title: "The effectiveness and side effects of pyridostigmine in the treatment of myasthenia gravis: a cross-sectional study."
    supports: SUPPORT
    snippet: "Of all patients currently using pyridostigmine, 91% reported side effects (vs. 55% in the control group)."
    explanation: While effective, pyridostigmine has high rate of side effects including GI symptoms.
  target_mechanisms:
  - target: Autoantibody-Mediated NMJ Dysfunction
    treatment_effect: MODULATES
    description: >-
      Pyridostigmine inhibits acetylcholinesterase at the neuromuscular junction,
      prolonging ACh availability and partially compensating for the reduced AChR
      density caused by autoantibody-mediated receptor internalization and complement
      destruction.
- name: Corticosteroids
  description: Prednisone for immunosuppression, mainstay of therapy.
  treatment_term:
    preferred_term: corticosteroid agent therapy
    term:
      id: NCIT:C122080
      label: Systemic Corticosteroid Therapy
  target_mechanisms:
  - target: Autoantibody-Mediated NMJ Dysfunction
    treatment_effect: INHIBITS
    description: >-
      Corticosteroids suppress the autoimmune B and T cell responses that drive
      AChR autoantibody production, progressively reducing the antibody burden
      at the neuromuscular junction.
  - target: Thymic Abnormalities
    treatment_effect: INHIBITS
    description: >-
      Corticosteroids suppress thymic inflammation and lymphoproliferation,
      dampening the autoreactive T cell activation that originates in the thymus.
- name: Thymectomy
  description: Surgical removal of thymus, improves outcomes in appropriate patients.
  treatment_term:
    preferred_term: thymectomy
    term:
      id: NCIT:C29894
      label: Thymectomy
  evidence:
  - reference: PMID:27509100
    reference_title: "Randomized Trial of Thymectomy in Myasthenia Gravis."
    supports: SUPPORT
    snippet: "Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001)"
    explanation: Landmark randomized trial demonstrates thymectomy improves clinical outcomes in nonthymomatous MG.
  - reference: PMID:27509100
    reference_title: "Randomized Trial of Thymectomy in Myasthenia Gravis."
    supports: SUPPORT
    snippet: "Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001)."
    explanation: Thymectomy reduces need for additional immunosuppression and hospitalizations.
  target_mechanisms:
  - target: Thymic Abnormalities
    treatment_effect: INHIBITS
    description: >-
      Thymectomy removes the hyperplastic or thymomatous thymus that harbors
      the autoreactive T cells and AChR-expressing myoid cells that initiate and
      sustain the AChR autoimmune response.
- name: Azathioprine
  description: Steroid-sparing immunosuppressant.
  treatment_term:
    preferred_term: immune suppressant agent therapy
    term:
      id: NCIT:C15261
      label: Immunosuppressive Therapy
  target_mechanisms:
  - target: Autoantibody-Mediated NMJ Dysfunction
    treatment_effect: INHIBITS
    description: >-
      Azathioprine, a purine antimetabolite, suppresses lymphocyte proliferation,
      reducing autoreactive B and T cell populations and thereby lowering AChR
      autoantibody production at the neuromuscular junction.
- name: Mycophenolate Mofetil
  description: Alternative immunosuppressant.
  treatment_term:
    preferred_term: immune suppressant agent therapy
    term:
      id: NCIT:C15261
      label: Immunosuppressive Therapy
  target_mechanisms:
  - target: Autoantibody-Mediated NMJ Dysfunction
    treatment_effect: INHIBITS
    description: >-
      Mycophenolate mofetil inhibits inosine monophosphate dehydrogenase,
      selectively suppressing lymphocyte proliferation and reducing AChR
      autoantibody production.
- name: Rituximab
  description: Anti-CD20 antibody, effective in refractory cases.
  treatment_term:
    preferred_term: immune suppressant agent therapy
    term:
      id: NCIT:C15261
      label: Immunosuppressive Therapy
  target_mechanisms:
  - target: Autoantibody-Mediated NMJ Dysfunction
    treatment_effect: INHIBITS
    description: >-
      Rituximab depletes CD20+ B cells and plasmablasts, reducing the pool of
      antibody-secreting cells and lowering AChR (or MuSK) autoantibody titers
      that mediate NMJ dysfunction.
- name: Eculizumab
  description: Complement inhibitor (anti-C5), approved for refractory AChR+ MG.
  treatment_term:
    preferred_term: complement 5 inhibitor agent therapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: complement inhibitor
      term:
        id: NCIT:C199456
        label: Complement Inhibitor
  evidence:
  - reference: PMID:29066163
    reference_title: "Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study."
    supports: SUPPORT
    snippet: "Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis."
    explanation: Phase 3 REGAIN trial evaluated eculizumab in refractory generalized MG.
  - reference: PMID:29066163
    reference_title: "Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study."
    supports: SUPPORT
    snippet: "Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group."
    explanation: Eculizumab reduced exacerbation rates compared to placebo.
  target_mechanisms:
  - target: Complement Activation
    treatment_effect: INHIBITS
    description: >-
      Eculizumab is a monoclonal antibody that binds complement component C5,
      blocking cleavage to C5a and C5b and preventing membrane attack complex
      formation at the neuromuscular junction.
- name: Plasma Exchange
  description: Rapid removal of antibodies, used for myasthenic crisis.
  evidence:
  - reference: PMID:21674519
    reference_title: "Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts."
    supports: SUPPORT
    snippet: "Plasma exchange (PLEX) produced improvement in 93%, whereas only 61% improved after intravenous immunoglobulin."
    explanation: Plasma exchange is highly effective, particularly in MuSK-MG where it outperforms IVIG.
  target_mechanisms:
  - target: Autoantibody-Mediated NMJ Dysfunction
    treatment_effect: INHIBITS
    description: >-
      Plasma exchange physically removes circulating AChR and MuSK autoantibodies
      from the bloodstream, rapidly reducing the antibody burden at the
      neuromuscular junction.
- name: Intravenous Immunoglobulin
  description: Immunomodulation, used for exacerbations and crisis.
  target_mechanisms:
  - target: Autoantibody-Mediated NMJ Dysfunction
    treatment_effect: INHIBITS
    description: >-
      IVIG modulates autoantibody activity via Fc receptor saturation and
      complement inhibition, reducing the effective titer of pathogenic AChR
      autoantibodies at the neuromuscular junction.
- name: Efgartigimod
  description: FcRn antagonist approved for generalized AChR-positive MG; reduces pathogenic IgG levels by blocking neonatal Fc receptor recycling.
  treatment_term:
    preferred_term: FcRn antagonist therapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:37602255
    reference_title: "FcRN receptor antagonists in the management of myasthenia gravis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Efgartigimod is already approved for the treatment of generalized MG"
    explanation: Review confirms FDA approval of efgartigimod for generalized MG.
  - reference: PMID:37602255
    reference_title: "FcRN receptor antagonists in the management of myasthenia gravis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      FcRn receptors prevent the catabolism of IgG by impeding their lysosomal
      degradation and facilitating their extracellular release at physiological
      pH, consequently extending the IgG half-life.
    explanation: >
      The research synthesis emphasized FcRn biology; this evidence links the
      treatment assertion to its mechanism of lowering pathogenic IgG.
  target_mechanisms:
  - target: Autoantibody-Mediated NMJ Dysfunction
    treatment_effect: INHIBITS
    description: >-
      Efgartigimod blocks the neonatal Fc receptor (FcRn), preventing IgG
      recycling and accelerating catabolism of pathogenic AChR autoantibodies,
      thereby reducing the antibody burden at the neuromuscular junction.
- name: Rozanolixizumab
  description: >-
    Subcutaneous FcRn antagonist for generalized myasthenia gravis in adults
    who are anti-AChR or anti-MuSK antibody positive; reduces pathogenic IgG
    via neonatal Fc receptor blockade.
  treatment_term:
    preferred_term: FcRn antagonist therapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:37059507
    reference_title: "Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We enrolled patients (aged ≥18 years) with acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) autoantibody-positive generalised myasthenia gravis"
    explanation: The registrational phase 3 trial enrolled both anti-AChR and anti-MuSK antibody-positive generalized MG, which is the population the treatment is indicated for.
  - reference: PMID:37059507
    reference_title: "Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rozanolixizumab showed clinically meaningful improvements in patient-reported and investigator-assessed outcomes in patients with generalised myasthenia gravis, for both 7 mg/kg and 10 mg/kg doses."
    explanation: Phase 3 efficacy result supporting rozanolixizumab as an active treatment for generalized MG.
  - reference: PMID:37602255
    reference_title: "FcRN receptor antagonists in the management of myasthenia gravis"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "rozanolixizumab is under review by health authorities"
    explanation: Historical regulatory context only - this 2023 review predates approval; the drug has since been approved for generalized MG, so this quote no longer describes current status.
  target_mechanisms:
  - target: Autoantibody-Mediated NMJ Dysfunction
    treatment_effect: INHIBITS
    description: >-
      Rozanolixizumab blocks FcRn to accelerate IgG catabolism, reducing
      circulating AChR autoantibody levels and lessening antibody-mediated
      disruption of neuromuscular transmission.
datasets:
- accession: geo:GSE233180
  title: Thymic B lineage cell landscape in Myasthenia gravis
  description: Here, we provide a comprehensive and unbiased atlas of hematopoietic cell colonization in thymi derived from 12 immunotherapy-naïve patients with early-onset AChR-Ab+ MG (EOMG) using single-cell RNA sequencing (scRNA‑seq).
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: SINGLE_CELL_RNA_SEQ
  sample_count: 24
  publication: PMID:40117520
  notes: Identified by GEO DataSets index search for Myasthenia Gravis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE227835
  title: Single-cell RNA-seq data of human PBMC from Myasthenia Gravis patients
  description: Myasthenia Gravis (MG) is a chronic autoimmune disorder characterized by severe muscle weakness. However, the seronegative MG patient subgroup, which accounts for about 15% of MG patients, remains challenging diagnosis, and the immunopathology is understudied. Therefore, we performed single-cell RNA-sequencing analysis by peripheral blood and plasma proteome analysis for the seronegative MG patients. Numerical abnormalities were observed in multiple immune cells including B-cells compared to healthy controls (HC) and correlated with disease activities.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: SINGLE_CELL_RNA_SEQ
  sample_count: 40
  publication: PMID:38711503
  notes: Identified by GEO DataSets index search for Myasthenia Gravis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE182038
  title: Elevated N-linked glycosylation of IgG variable regions in myasthenia gravis disease subtypes
  description: Elevated N-linked glycosylation of immunoglobulin G variable regions (IgG-VN-Glyc) is an emerging molecular phenotype associated with autoimmune disorders. To test the broader specificity of elevated IgG-VN-Glyc, we studied patients with distinct subtypes of myasthenia gravis (MG), a B cell-mediated autoimmune disease. Our experimental design included adaptive immune receptor repertoire sequencing to quantify and characterize N-glycosylation sites in the global B cell receptor repertoire, proteomics to examine glycosylation patterns of the circulating IgG, and production of human-derived recombinant autoantibodies, which were studied with mass spectrometry and antigen binding assays to confi...
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 31
  publication: PMID:34544801
  notes: Identified by GEO DataSets index search for Myasthenia Gravis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: ega:EGAS00001003462
  title: Whole genome sequencing of 25 South African individuals with myasthenia gravis
  description: This study investigated the genetic basis of an ophthalmoplegic subphenotype of MG (OP-MG) which occurs in a proportion of myasthenics with juvenile symptom onset and African genetic ancestry. This OP-MG subphenotype is characterised by treatment resistant weakness of the extraocular muscles (EOMs) and the pathogenetic mechanism(s) underlying its development is unknown. The aim of this study was to use a hypothesis-generating genome-wide case-control analysis to identify candidate OP-MG susceptibility genes and pathways.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  publication: PMID:30881381
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Myasthenia Gravis"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: dbgap:phs000726
  title: Genome-wide Association Study of Myasthenia Gravis
  description:  The purpose of this project was to conduct a genome-wide associate study to search for the genetic factors that predispose to myasthenia gravis. The rationale for this study lies in the fact that, although the immunological and physiological processes affecting the neuromuscular junctions of myasthenia gravis patients are well understood, the spectrum of genetic factors that predispose to myasthenia gravis and influence its disease manifestations are not well known.
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Myasthenia Gravis"). Retrieved 2026-08-02.
references:
- reference: PMID:38789789
  title: Treating myasthenia gravis beyond the eye clinic
  findings: []
  found_in:
  - Myasthenia_Gravis-deep-research-cyberian-codex.md
  - Myasthenia_Gravis-deep-research-falcon.md
- reference: PMID:39537604
  title: Genome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction
  findings: []
  found_in:
  - Myasthenia_Gravis-deep-research-cyberian-codex.md
  - Myasthenia_Gravis-deep-research-falcon.md
- reference: DOI:10.1080/1744666x.2022.2082946
  title: Role of complement, anti-complement therapeutics, and other targeted immunotherapies in myasthenia gravis
  findings: []
  found_in:
  - Myasthenia_Gravis-deep-research-cyberian-codex.md
  - Myasthenia_Gravis-deep-research-falcon.md
- reference: DOI:10.1136/jnnp-2023-333097
  title: 'Epidemiology of myasthenia gravis in Denmark, Finland and Sweden: a population-based observational study'
  findings: []
  found_in:
  - Myasthenia_Gravis-deep-research-cyberian-codex.md
  - Myasthenia_Gravis-deep-research-falcon.md
- reference: DOI:10.1172/jci179742
  title: 'Myasthenia gravis: the future is here'
  findings: []
  found_in:
  - Myasthenia_Gravis-deep-research-cyberian-codex.md
  - Myasthenia_Gravis-deep-research-falcon.md
- reference: DOI:10.3389/fimmu.2023.1110499
  title: Inflammation and autoimmune myasthenia gravis
  findings: []
  found_in:
  - Myasthenia_Gravis-deep-research-cyberian-codex.md
  - Myasthenia_Gravis-deep-research-falcon.md
- reference: PMID:37602255
  title: FcRN receptor antagonists in the management of myasthenia gravis
  findings: []
  found_in:
  - Myasthenia_Gravis-deep-research-cyberian-codex.md
  - Myasthenia_Gravis-deep-research-falcon.md
- reference: DOI:10.3389/fneur.2024.1339167
  title: Epidemiology of myasthenia gravis in the United States
  findings: []
  found_in:
  - Myasthenia_Gravis-deep-research-cyberian-codex.md
  - Myasthenia_Gravis-deep-research-falcon.md
- reference: DOI:10.3390/cells13060556
  title: MuSK Myasthenia Gravis-Potential Pathomechanisms and Treatment Directed against Specific Targets
  findings: []
  found_in:
  - Myasthenia_Gravis-deep-research-cyberian-codex.md
  - Myasthenia_Gravis-deep-research-falcon.md
- reference: DOI:10.3390/ijms22115755
  title: Fc-Receptor Targeted Therapies for the Treatment of Myasthenia gravis
  findings: []
  found_in:
  - Myasthenia_Gravis-deep-research-cyberian-codex.md
  - Myasthenia_Gravis-deep-research-falcon.md
📚

References & Deep Research

References

10
PMID:38789789
Treating myasthenia gravis beyond the eye clinic
No top-level findings curated for this source.
PMID:39537604
Genome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction
No top-level findings curated for this source.
DOI:10.1080/1744666x.2022.2082946
Role of complement, anti-complement therapeutics, and other targeted immunotherapies in myasthenia gravis
No top-level findings curated for this source.
DOI:10.1136/jnnp-2023-333097
Epidemiology of myasthenia gravis in Denmark, Finland and Sweden: a population-based observational study
No top-level findings curated for this source.
DOI:10.1172/jci179742
Myasthenia gravis: the future is here
No top-level findings curated for this source.
DOI:10.3389/fimmu.2023.1110499
Inflammation and autoimmune myasthenia gravis
No top-level findings curated for this source.
PMID:37602255
FcRN receptor antagonists in the management of myasthenia gravis
No top-level findings curated for this source.
DOI:10.3389/fneur.2024.1339167
Epidemiology of myasthenia gravis in the United States
No top-level findings curated for this source.
DOI:10.3390/cells13060556
MuSK Myasthenia Gravis-Potential Pathomechanisms and Treatment Directed against Specific Targets
No top-level findings curated for this source.
DOI:10.3390/ijms22115755
Fc-Receptor Targeted Therapies for the Treatment of Myasthenia gravis
No top-level findings curated for this source.

Deep Research

2
Disorder ▸

Disorder

  • Name: Myasthenia Gravis
  • Category: Autoimmune
  • Existing deep-research providers: falcon
  • Existing evidence reference count in YAML: 26

Key Pathophysiology Nodes

  • Autoantibody-Mediated NMJ Dysfunction
  • Complement Activation
  • Thymic Abnormalities
  • Deep research literature mapping

Citation Inventory (for evidence mapping)

  • DOI:10.1038/s41433-024-03133-x
  • DOI:10.1038/s41467-024-53595-6
  • DOI:10.1080/1744666x.2022.2082946
  • DOI:10.1136/jnnp-2023-333097
  • DOI:10.1172/jci179742
  • DOI:10.3389/fimmu.2023.1110499
  • DOI:10.3389/fneur.2023.1229112
  • DOI:10.3389/fneur.2024.1339167
  • DOI:10.3390/cells13060556
  • DOI:10.3390/ijms22115755
Falcon ▸
Disease Pathophysiology Research Report
Edison Scientific Literature 23 citations 2025-12-18T09:54:07.915621

Disease Pathophysiology Research Report

Target Disease - Disease Name: Myasthenia Gravis (MG) - MONDO ID: MONDO:0005041 - Category: Autoimmune

Pathophysiology description Myasthenia gravis is a prototypic antibody-mediated autoimmune synaptopathy of the neuromuscular junction (NMJ). In AChR-antibody–positive MG (the most common subtype), IgG1/IgG3 antibodies drive three principal mechanisms: (i) classical complement pathway activation culminating in membrane attack complex (MAC)–mediated injury with loss of postsynaptic folds and AChR-rich membrane, (ii) antigenic modulation with cross-linking–induced endocytosis and degradation of AChR, and (iii) direct functional blockade of the acetylcholine binding site. These mechanisms reduce the safety factor for neuromuscular transmission and produce fatigable weakness (Journal of Clinical Investigation, Jun 2024, https://doi.org/10.1172/jci179742). Complement C5 inhibition clinically validates the centrality of MAC injury in AChR-MG (eculizumab, ravulizumab, zilucoplan) (JCI 2024; Expert Rev Clin Immunol 2022, https://doi.org/10.1080/1744666X.2022.2082946). MuSK-MG is mechanistically distinct: pathogenic antibodies are predominantly IgG4, functionally monovalent after Fab-arm exchange, and block LRP4–MuSK interaction and downstream phosphorylation cascades required for AChR clustering; complement fixation is minimal in MuSK-MG. LRP4 antibodies can activate complement (typically IgG1) and also interfere with agrin–LRP4 signaling, disrupting AChR clustering (Eye, May 2024, https://doi.org/10.1038/s41433-024-03133-x; Cells, Mar 2024, https://doi.org/10.3390/cells13060556). Seronegative MG (by routine assays) is heterogeneous and includes patients with low-affinity/clustered AChR antibodies, LRP4/agrin antibodies, or as-yet-undetected reactivities (JCI 2024).

Thymic autoimmunity is characteristic of early-onset AChR-MG, with thymic follicular hyperplasia, ectopic germinal centers, and dysregulated T–B collaboration (increased T follicular helper cells, reduced Treg function) that foster intrathymic affinity maturation and long-lived autoantibody responses. Type I interferon–rich signatures, CXCL13, and BAFF pathways are implicated in perpetuating the thymic autoimmune niche. Thymoma-associated MG has distinct serology and autoantibody spectra, whereas MuSK-MG generally lacks prominent thymic pathology (JCI 2024; Frontiers in Immunology, Jan 2023, https://doi.org/10.3389/fimmu.2023.1110499; Frontiers in Neurology, Aug 2023, https://doi.org/10.3389/fneur.2023.1229112).

Therapeutic mechanism-of-action (MOA) validation underscores these pathways: terminal complement C5 inhibitors reduce MAC injury and improve strength in refractory AChR-MG, while FcRn antagonists accelerate pathogenic IgG catabolism, lowering circulating autoantibody levels and improving outcomes across antibody-defined subtypes; both approaches have translated to approved therapies (Frontiers in Neurology 2023; JCI 2024; Expert Rev Clin Immunol 2022). (kaminski2024myastheniagravisthe pages 2-4, jacob2024treatingmyastheniagravis pages 1-2, bhandari2023fcrnreceptorantagonists pages 1-2, keller2022fcreceptortargetedtherapies pages 2-3)

Key concepts and definitions - AChR-MG: IgG1/IgG3-mediated disease marked by complement activation, AChR internalization, and receptor blockade at the postsynaptic membrane. (kaminski2024myastheniagravisthe pages 2-4, jacob2024treatingmyastheniagravis pages 1-2) - MuSK-MG: IgG4-predominant autoimmunity with blocking of LRP4–MuSK signaling and impaired AChR clustering; minimal complement activation; often responds well to B cell depletion. (dziadkowiak2024muskmyastheniagravis—potential pages 13-14, jacob2024treatingmyastheniagravis pages 1-2) - LRP4-MG: Antibodies disrupt agrin–LRP4–MuSK pathway and can fix complement; may coexist with other autoantibodies. (jacob2024treatingmyastheniagravis pages 1-2) - Seronegative MG: Heterogeneous; includes low-affinity clustered AChR antibodies or antibodies to LRP4/agrin not detected by standard assays. (kaminski2024myastheniagravisthe pages 2-4) - FcRn: Endosomal receptor that rescues IgG from lysosomal degradation; therapeutic blockade reduces pathogenic IgG burden systemically. (bhandari2023fcrnreceptorantagonists pages 1-2)

Recent developments and latest research (2023–2024) - Genetics: A large 2024 GWAS/meta-analysis identified multiple genome-wide significant loci, clarified HLA class II influences, and demonstrated polygenic risk prediction in MG, with distinct early- vs late-onset associations (Nature Communications, Nov 2024, https://doi.org/10.1038/s41467-024-53595-6). Clinical overviews also emphasize PTPN22 and CTLA4 associations across subgroups (JCI 2024). (kaminski2024myastheniagravisthe pages 2-4) - Epidemiology: Contemporary population-based studies show increasing incidence and prevalence in high-income countries, with strong age and sex effects. Nordic registry data (JNNP, Mar 2024) and US claims analyses (Frontiers in Neurology, Feb 2024) quantify rising prevalence and stable to modestly rising incidence, particularly in older adults. (, ) - ncRNA/epigenetics and inflammation: Reviews highlight altered microRNA profiles in thymus and blood, type I interferon signaling, BAFF/Tfh axes, and inflammatory cytokine networks contributing to MG pathogenesis and heterogeneity, supporting biomarker-guided and epigenetic-targeting strategies (Frontiers in Immunology, Jan 2023; Eye, 2024). (huda2023inflammationandautoimmune pages 1-2, jacob2024treatingmyastheniagravis pages 1-2) - Therapeutics: FcRn inhibitors (efgartigimod, rozanolixizumab) and complement C5 inhibitors (eculizumab, ravulizumab, zilucoplan) consolidate mechanism-based treatment and enable earlier, targeted intervention strategies (Frontiers in Neurology 2023; Expert Rev Clin Immunol 2022; JCI 2024). (bhandari2023fcrnreceptorantagonists pages 1-2, keller2022fcreceptortargetedtherapies pages 2-3, kaminski2024myastheniagravisthe pages 2-4)

Current applications and real-world implementations - Complement inhibition (C5): Reduces MAC formation at the NMJ, directly addressing complement-mediated postsynaptic injury validated in AChR-MG. Clinical adoption for refractory generalized AChR-MG has been established (Expert Rev Clin Immunol 2022). (keller2022fcreceptortargetedtherapies pages 2-3) - FcRn antagonism: Lowers total IgG including pathogenic subclasses and improves clinical scores across subtypes; approved agents are increasingly used in cycles with monitoring of symptom trajectories (Frontiers in Neurology 2023). (bhandari2023fcrnreceptorantagonists pages 1-2) - B cell–directed therapy: Particularly impactful in MuSK-MG, aligning with IgG4/plasmablast biology and limited complement involvement (Cells 2024; Eye 2024). (dziadkowiak2024muskmyastheniagravis—potential pages 13-14, jacob2024treatingmyastheniagravis pages 1-2)

Expert opinions and analysis (authoritative sources) - Kaminski et al. (JCI, 2024) synthesize mechanistic, genetic, and therapeutic advances, reinforcing three canonical AChR-MG mechanisms at the NMJ, detailing subtype distinctions, and highlighting precision therapeutics (https://doi.org/10.1172/jci179742). (kaminski2024myastheniagravisthe pages 2-4, kaminski2024myastheniagravisthe pages 10-10) - Dalakas (Expert Rev Clin Immunol, 2022) argues complement and FcRn pathways are central, with clinical trial success translating to practice for refractory MG (https://doi.org/10.1080/1744666X.2022.2082946). (keller2022fcreceptortargetedtherapies pages 2-3) - Bhandari & Bril (Frontiers in Neurology, 2023) review FcRn biology/PK-PD and MG indications, supporting real-world utilization and safety (https://doi.org/10.3389/fneur.2023.1229112). (bhandari2023fcrnreceptorantagonists pages 1-2)

Relevant statistics and data (recent studies) - GWAS/meta-analysis (Nature Communications, 2024): 5708 MG cases/432,028 controls plus replication; 11 loci; PRS explained ~4.2% variance, with HLA signals showing inverse effects by age at onset (Nov 2024) (https://doi.org/10.1038/s41467-024-53595-6). (kaminski2024myastheniagravisthe pages 2-4) - Nordic epidemiology (JNNP, 2024): Incidence 1.3–1.7 per 100,000; prevalence ~18.6–23.4 per 100,000; standardized mortality ratios 1.20–1.32; rising prevalence over 2000–2020 (Mar 2024, https://doi.org/10.1136/jnnp-2023-333097). () - US epidemiology (Frontiers in Neurology, 2024): Age- and sex-standardized incidence ~68.5/million person-years (commercial/Medicare); prevalence ~316/million (2017), estimating ~82,715 adults living with MG in 2021 (Feb 2024, https://doi.org/10.3389/fneur.2024.1339167). ()

Core Pathophysiology (mechanisms, pathways, cells) - Primary mechanisms at the NMJ - Complement-mediated MAC injury (classical pathway via IgG1/IgG3 anti-AChR) leading to synaptic membrane loss and reduced safety factor (JCI 2024; Eye 2024). (kaminski2024myastheniagravisthe pages 2-4, jacob2024treatingmyastheniagravis pages 1-2) - Antigenic modulation and receptor internalization of AChR, reducing receptor density (JCI 2024; Frontiers in Immunology 2023). (kaminski2024myastheniagravisthe pages 2-4, huda2023inflammationandautoimmune pages 1-2) - Blockade of ACh–AChR interaction and disruption of rapsyn-stabilized clusters (JCI 2024). (kaminski2024myastheniagravisthe pages 2-4) - Agrin–LRP4–MuSK pathway blockade by IgG4 anti-MuSK (non–complement fixing) and IgG1 anti-LRP4, impairing AChR clustering (Eye 2024; Cells 2024). (jacob2024treatingmyastheniagravis pages 1-2, dziadkowiak2024muskmyastheniagravis—potential pages 13-14)

  • Dysregulated molecular/cellular pathways
  • Complement activation and MAC assembly in AChR-MG; therapeutic anti-C5 validation (Expert Rev Clin Immunol 2022). (keller2022fcreceptortargetedtherapies pages 2-3)
  • FcRn-mediated IgG recycling: therapeutic antagonism lowers IgG, supporting a causal role for circulating IgG autoantibodies broadly in MG (Frontiers in Neurology 2023). (bhandari2023fcrnreceptorantagonists pages 1-2)

  • Thymic ectopic germinal centers (GCs), Tfh expansion, BAFF enrichment, and type I IFN signatures that sustain intrathymic B cell activation and autoreactive T cell priming; weaker/thymus-sparse signature in MuSK-MG (JCI 2024; Frontiers in Immunology 2023). (kaminski2024myastheniagravisthe pages 2-4, huda2023inflammationandautoimmune pages 1-2)

  • Immune cell processes

  • B cell activation, class-switch, and plasmablast/plasma cell antibody production (intrathymic and peripheral) (JCI 2024; Frontiers in Immunology 2023). (kaminski2024myastheniagravisthe pages 2-4, huda2023inflammationandautoimmune pages 1-2)
  • Tfh/Tfr imbalance and reduced Treg function facilitating GC reactions (JCI 2024; Frontiers in Immunology 2023). (kaminski2024myastheniagravisthe pages 2-4, huda2023inflammationandautoimmune pages 1-2)
  • Antigen presentation by medullary thymic epithelial cells (mTECs) and dendritic cells, with tolerance failure in EOMG (Frontiers in Neurology 2023). (bhandari2023fcrnreceptorantagonists pages 1-2)

Key Molecular Players (HGNC genes/proteins; cell types; anatomical sites; chemicals) - Autoantigens/complex - AChR subunits (HGNC: CHRNA1, CHRNB1), rapsyn (HGNC: RAPSN), DOK7 (HGNC: DOK7) (JCI 2024). (kaminski2024myastheniagravisthe pages 2-4) - MUSK (HGNC: 7517), LRP4 (HGNC: 6697), AGRN (HGNC: 329) central to clustering and synaptogenesis (Eye 2024; Cells 2024). (jacob2024treatingmyastheniagravis pages 1-2, dziadkowiak2024muskmyastheniagravis—potential pages 13-14) - Immune genes (selected associations) - HLA class II alleles (e.g., HLA-DRB1, HLA-DQB1) with subtype/age-of-onset effects; CTLA4 and PTPN22 highlighted in clinical overviews (Nature Comm 2024; JCI 2024). (kaminski2024myastheniagravisthe pages 2-4) - Cell types (CL ontology) - B cell (CL:0000236), plasmablast (CL:0000980), T follicular helper cell (CL:0000914), regulatory T cell (CL:0000815), dendritic cell (CL:0000451), medullary thymic epithelial cell (CL:0000786) (Frontiers in Immunology 2023; JCI 2024). (huda2023inflammationandautoimmune pages 1-2, kaminski2024myastheniagravisthe pages 2-4) - Anatomical locations (UBERON) - Neuromuscular junction (UBERON:0007200), skeletal muscle tissue (UBERON:0001134), thymus (UBERON:0002370) (JCI 2024; Eye 2024). (kaminski2024myastheniagravisthe pages 2-4, jacob2024treatingmyastheniagravis pages 1-2) - Chemical entities (ChEBI) - Acetylcholine (CHEBI:15355), immunoglobulin G (CHEBI:16991); complement component C5 protein targeted by therapeutics (mechanistic) (Expert Rev Clin Immunol 2022). (keller2022fcreceptortargetedtherapies pages 2-3)

Biological Processes for GO annotation (disrupted in MG) - Complement activation, classical pathway (GO:0006958); membrane attack complex assembly (component of complement activation) (AChR-MG) (JCI 2024; Expert Rev Clin Immunol 2022). (kaminski2024myastheniagravisthe pages 2-4, keller2022fcreceptortargetedtherapies pages 2-3) - Receptor-mediated endocytosis (GO:0006898) of AChR (antigenic modulation) (JCI 2024). (kaminski2024myastheniagravisthe pages 2-4) - Cholinergic synaptic transmission (GO:0007271) and neuromuscular junction development (GO:0007528) (disrupted by agrin–LRP4–MuSK blockade) (Eye 2024; Cells 2024). (jacob2024treatingmyastheniagravis pages 1-2, dziadkowiak2024muskmyastheniagravis—potential pages 13-14) - B cell activation (GO:0042113), germinal center formation (GO:0006955, immune process), T cell activation (GO:0042110), Tfh cell differentiation (GO:0002292) (thymic hyperplasia) (Frontiers in Immunology 2023; JCI 2024). (huda2023inflammationandautoimmune pages 1-2, kaminski2024myastheniagravisthe pages 2-4) - Type I interferon signaling pathway (GO:0060337) and cytokine-mediated signaling (GO:0019221) in thymic microenvironment (Frontiers in Immunology 2023). (huda2023inflammationandautoimmune pages 1-2)

Cellular Components (where key processes occur) - Postsynaptic membrane (GO:0045211) and synaptic basal lamina/extracellular matrix (basement membrane, GO:0005604) at NMJ—sites of AChR and agrin–LRP4–MuSK signaling (Eye 2024; JCI 2024). (jacob2024treatingmyastheniagravis pages 1-2, kaminski2024myastheniagravisthe pages 2-4) - Membrane attack complex (GO:0005579) on the postsynaptic membrane (Expert Rev Clin Immunol 2022; JCI 2024). (keller2022fcreceptortargetedtherapies pages 2-3, kaminski2024myastheniagravisthe pages 2-4) - Early/late endosomes and lysosomes (GO:0005768; GO:0005764) mediating AChR internalization and FcRn-dependent IgG recycling (Frontiers in Neurology 2023). (bhandari2023fcrnreceptorantagonists pages 1-2) - Thymic medulla and germinal center–like niches (thymic follicular hyperplasia) as intrathymic sites of autoimmunity (Frontiers in Immunology 2023; JCI 2024). (huda2023inflammationandautoimmune pages 1-2, kaminski2024myastheniagravisthe pages 2-4)

Disease progression (sequence from trigger to clinical phenotype) - Predisposition and trigger: Polygenic susceptibility (HLA class II, immune-regulatory loci) and environmental/inflammatory triggers (e.g., type I IFN–rich milieu) prime breakdown of central tolerance in the thymus for EOMG. (kaminski2024myastheniagravisthe pages 2-4, huda2023inflammationandautoimmune pages 1-2) - Intrathymic autoimmunity: mTEC/dendritic cell antigen presentation of AChR subunits and myoid-cell antigens with GC formation, Tfh help, BAFF signaling, and class-switched B cell responses. (huda2023inflammationandautoimmune pages 1-2, bhandari2023fcrnreceptorantagonists pages 1-2) - Peripheral effector phase: Circulating IgG autoantibodies reach NMJ; in AChR-MG, complement activation and receptor internalization reduce neuromuscular safety factor; in MuSK-/LRP4-MG, impaired AChR clustering further reduces transmission. (kaminski2024myastheniagravisthe pages 2-4, jacob2024treatingmyastheniagravis pages 1-2, dziadkowiak2024muskmyastheniagravis—potential pages 13-14) - Clinical manifestation: Fluctuating, fatigable weakness with ocular, bulbar, respiratory, and limb involvement according to antibody specificity and disease burden; crises occur with severe bulbar/respiratory involvement. (jacob2024treatingmyastheniagravis pages 1-2)

Phenotypic manifestations and mechanism links (HP terms) - Fatigable muscle weakness (HP:0003701): Reduced NMJ safety factor from MAC injury and AChR loss (AChR-MG) or from impaired AChR clustering (MuSK-/LRP4-MG) (JCI 2024; Eye 2024). (kaminski2024myastheniagravisthe pages 2-4, jacob2024treatingmyastheniagravis pages 1-2) - Ptosis (HP:0000508) and diplopia (HP:0000651): Extraocular NMJ involvement; ocular MG commonly due to AChR antibodies (Eye 2024). (jacob2024treatingmyastheniagravis pages 1-2) - Dysphagia (HP:0002015), dysarthria (HP:0001260), and respiratory failure (HP:0002878): Bulbar/respiratory muscle NMJ failure; severe in some MuSK-MG and generalized AChR-MG (Eye 2024). (jacob2024treatingmyastheniagravis pages 1-2)

Gene/protein annotations (selected; HGNC and ontology mapping) - CHRNA1 (HGNC:1956) and CHRNB1 (HGNC:1959): AChR subunits; processes: cholinergic synaptic transmission (GO:0007271), receptor-mediated endocytosis (GO:0006898); component: postsynaptic membrane (GO:0045211). (kaminski2024myastheniagravisthe pages 2-4) - MUSK (HGNC:7517): Receptor tyrosine kinase for NMJ maintenance; processes: NMJ development (GO:0007528); component: postsynaptic membrane (GO:0045211). (dziadkowiak2024muskmyastheniagravis—potential pages 13-14, jacob2024treatingmyastheniagravis pages 1-2) - LRP4 (HGNC:6697): Agrin co-receptor; processes: synapse organization (GO:0050808); component: extracellular region/basal lamina. (jacob2024treatingmyastheniagravis pages 1-2) - AGRN (HGNC:329): Ligand driving AChR clustering; processes: synapse organization; component: synaptic cleft/extracellular matrix. (jacob2024treatingmyastheniagravis pages 1-2) - HLA-DRB1/DQB1 (HGNC:4948/3115), CTLA4 (HGNC:2505), PTPN22 (HGNC:9653): Genetic susceptibility; processes: antigen presentation (GO:0019882), T cell activation (GO:0042110). (kaminski2024myastheniagravisthe pages 2-4)

Cell type involvement (CL) and anatomical locations (UBERON) - B cells (CL:0000236) and plasmablasts (CL:0000980): Autoantibody production in thymic GCs and periphery (UBERON:0002370, thymus; UBERON:0007200, NMJ effector site) (Frontiers in Immunology 2023; JCI 2024). (huda2023inflammationandautoimmune pages 1-2, kaminski2024myastheniagravisthe pages 2-4) - Tfh (CL:0000914)/Tfr and Tregs (CL:0000815): GC support vs regulation; imbalance favors autoimmunity (Frontiers in Immunology 2023). (huda2023inflammationandautoimmune pages 1-2) - Dendritic cells (CL:0000451) and mTECs (CL:0000786): Central tolerance and antigen presentation in thymus (Frontiers in Neurology 2023). (bhandari2023fcrnreceptorantagonists pages 1-2)

Chemical entities (CHEBI) and therapeutics (mechanistic tie-ins) - Acetylcholine (CHEBI:15355): Neurotransmitter whose postsynaptic signaling is impaired by AChR loss/blockade (Eye 2024). (jacob2024treatingmyastheniagravis pages 1-2) - IgG (CHEBI:16991): Pathogenic effector molecule; subclasses dictate complement activity (IgG1/3) vs blocking (IgG4) (JCI 2024; Frontiers in Neurology 2023). (kaminski2024myastheniagravisthe pages 2-4, bhandari2023fcrnreceptorantagonists pages 1-2) - Complement C5 (protein target): Blockade prevents MAC formation at NMJ in AChR-MG, validating complement’s causal role (Expert Rev Clin Immunol 2022). (keller2022fcreceptortargetedtherapies pages 2-3)

Evidence items with PMIDs/DOIs/URLs (recent, prioritized) - Kaminski HJ et al. Myasthenia gravis: the future is here. Journal of Clinical Investigation. Jun 2024. DOI: 10.1172/jci179742; URL: https://doi.org/10.1172/jci179742 (supports NMJ mechanisms, subtypes, genetics, therapeutics). (kaminski2024myastheniagravisthe pages 2-4, kaminski2024myastheniagravisthe pages 10-10) - Dalakas MC. Role of complement and targeted immunotherapies in MG. Expert Review of Clinical Immunology. Jun 2022. DOI: 10.1080/1744666X.2022.2082946; URL: https://doi.org/10.1080/1744666X.2022.2082946 (validates complement inhibition). (keller2022fcreceptortargetedtherapies pages 2-3) - Bhandari V, Bril V. FcRn receptor antagonists in MG. Frontiers in Neurology. Aug 2023. DOI: 10.3389/fneur.2023.1229112; URL: https://doi.org/10.3389/fneur.2023.1229112 (FcRn biology and clinical use). (bhandari2023fcrnreceptorantagonists pages 1-2) - Jacob S. Treating myasthenia gravis beyond the eye clinic. Eye. May 2024. DOI: 10.1038/s41433-024-03133-x; URL: https://doi.org/10.1038/s41433-024-03133-x (subtype mechanisms, clinical correlations). (jacob2024treatingmyastheniagravis pages 1-2) - Dziadkowiak E et al. MuSK Myasthenia Gravis—Mechanisms and targeted treatment. Cells. Mar 2024. DOI: 10.3390/cells13060556; URL: https://doi.org/10.3390/cells13060556 (MuSK IgG4 pathology). (dziadkowiak2024muskmyastheniagravis—potential pages 13-14) - Huda R. Inflammation and autoimmune MG. Frontiers in Immunology. Jan 2023. DOI: 10.3389/fimmu.2023.1110499; URL: https://doi.org/10.3389/fimmu.2023.1110499 (thymic inflammation, Tfh/BAFF/IFN). (huda2023inflammationandautoimmune pages 1-2) - Braun A et al. Genome-wide meta-analysis of MG. Nature Communications. Nov 2024. DOI: 10.1038/s41467-024-53595-6; URL: https://doi.org/10.1038/s41467-024-53595-6 (genetics, PRS). (kaminski2024myastheniagravisthe pages 2-4) - Vissing J et al. Epidemiology of MG in Denmark, Finland, Sweden. JNNP. Mar 2024. DOI: 10.1136/jnnp-2023-333097; URL: https://doi.org/10.1136/jnnp-2023-333097 (epidemiology). () - Ye Y et al. Epidemiology of MG in the USA. Frontiers in Neurology. Feb 2024. DOI: 10.3389/fneur.2024.1339167; URL: https://doi.org/10.3389/fneur.2024.1339167 (epidemiology). ()

Direct quotes (supporting key statements) - “AChR antibodies act via three established mechanisms: complement activation with MAC formation… antigenic modulation… and direct blockade of the ACh binding site” (JCI 2024) (kaminski2024myastheniagravisthe pages 2-4). - “MuSK autoantibodies are predominantly IgG4… block the binding site for LRP4 on MuSK, thereby inhibiting the downstream phosphorylation pathway and compromising the formation of AChR clusters” (Cells 2024) (dziadkowiak2024muskmyastheniagravis—potential pages 13-14). - “FcRn receptors prevent the catabolism of IgG… blocking the FcRn… leading to outcomes similar to those achieved through plasma exchange” (Frontiers in Neurology 2023) (bhandari2023fcrnreceptorantagonists pages 1-2).

Structured ontology annotations for knowledge base - Disease: Myasthenia gravis (MONDO:0005041) - Genes/Proteins (HGNC): CHRNA1, CHRNB1, RAPSN, DOK7, MUSK, LRP4, AGRN, HLA-DRB1, HLA-DQB1, CTLA4, PTPN22 (kaminski2024myastheniagravisthe pages 2-4, jacob2024treatingmyastheniagravis pages 1-2, dziadkowiak2024muskmyastheniagravis—potential pages 13-14) - GO Processes: complement activation, classical pathway (GO:0006958); receptor-mediated endocytosis (GO:0006898); cholinergic synaptic transmission (GO:0007271); neuromuscular junction development (GO:0007528); B cell activation (GO:0042113); T cell activation (GO:0042110); type I interferon signaling (GO:0060337) (kaminski2024myastheniagravisthe pages 2-4, keller2022fcreceptortargetedtherapies pages 2-3, huda2023inflammationandautoimmune pages 1-2, jacob2024treatingmyastheniagravis pages 1-2) - Cellular Components: postsynaptic membrane (GO:0045211); membrane attack complex (GO:0005579); endosome (GO:0005768); lysosome (GO:0005764) (kaminski2024myastheniagravisthe pages 2-4, keller2022fcreceptortargetedtherapies pages 2-3, bhandari2023fcrnreceptorantagonists pages 1-2) - Cell Types (CL): B cell (CL:0000236); plasmablast (CL:0000980); Tfh (CL:0000914); Treg (CL:0000815); dendritic cell (CL:0000451); mTEC (CL:0000786) (huda2023inflammationandautoimmune pages 1-2, bhandari2023fcrnreceptorantagonists pages 1-2) - Anatomical Sites (UBERON): neuromuscular junction (UBERON:0007200); skeletal muscle tissue (UBERON:0001134); thymus (UBERON:0002370) (jacob2024treatingmyastheniagravis pages 1-2, kaminski2024myastheniagravisthe pages 2-4) - Chemical Entities (ChEBI): acetylcholine (CHEBI:15355); immunoglobulin G (CHEBI:16991) (jacob2024treatingmyastheniagravis pages 1-2, bhandari2023fcrnreceptorantagonists pages 1-2) - Phenotypes (HP): fatigable muscle weakness (HP:0003701); ptosis (HP:0000508); diplopia (HP:0000651); dysphagia (HP:0002015); dysarthria (HP:0001260); respiratory failure (HP:0002878) (jacob2024treatingmyastheniagravis pages 1-2)

Notes and limitations - Detailed thymic single-cell and spatial transcriptomic data, and comprehensive ncRNA catalogs, while summarized in reviews, require additional primary sources for subtype-specific differential expression beyond the scope of the citations gathered herein (Frontiers in Immunology 2023; JCI 2024). (huda2023inflammationandautoimmune pages 1-2, kaminski2024myastheniagravisthe pages 2-4)

Citations - Mechanistic claims at the NMJ: (kaminski2024myastheniagravisthe pages 2-4, jacob2024treatingmyastheniagravis pages 1-2, keller2022fcreceptortargetedtherapies pages 2-3) - MuSK/LRP4 subclass and signaling: (dziadkowiak2024muskmyastheniagravis—potential pages 13-14, jacob2024treatingmyastheniagravis pages 1-2) - Thymic pathology and immune subsets: (huda2023inflammationandautoimmune pages 1-2, kaminski2024myastheniagravisthe pages 2-4, bhandari2023fcrnreceptorantagonists pages 1-2) - Therapeutic mechanistic validation (C5, FcRn): (keller2022fcreceptortargetedtherapies pages 2-3, bhandari2023fcrnreceptorantagonists pages 1-2, kaminski2024myastheniagravisthe pages 2-4) - Genetics (2024 GWAS/meta): (kaminski2024myastheniagravisthe pages 2-4) - Epidemiology (2024): (, )

References

  1. (kaminski2024myastheniagravisthe pages 2-4): Henry J. Kaminski, Patricia Sikorski, S. Isabel Coronel, and Linda L. Kusner. Myasthenia gravis: the future is here. Journal of Clinical Investigation, Jun 2024. URL: https://doi.org/10.1172/jci179742, doi:10.1172/jci179742. This article has 70 citations and is from a highest quality peer-reviewed journal.

  2. (jacob2024treatingmyastheniagravis pages 1-2): Saiju Jacob. Treating myasthenia gravis beyond the eye clinic. Eye, 38:2422-2436, May 2024. URL: https://doi.org/10.1038/s41433-024-03133-x, doi:10.1038/s41433-024-03133-x. This article has 6 citations and is from a peer-reviewed journal.

  3. (bhandari2023fcrnreceptorantagonists pages 1-2): Vinaya Bhandari and Vera Bril. Fcrn receptor antagonists in the management of myasthenia gravis. Frontiers in Neurology, Aug 2023. URL: https://doi.org/10.3389/fneur.2023.1229112, doi:10.3389/fneur.2023.1229112. This article has 33 citations and is from a peer-reviewed journal.

  4. (keller2022fcreceptortargetedtherapies pages 2-3): Christian W. Keller, Marc Pawlitzki, Heinz Wiendl, and Jan Lünemann. Fc-receptor targeted therapies for the treatment of myasthenia gravis. International Journal of Molecular Sciences, May 2022. URL: https://doi.org/10.3390/ijms22115755, doi:10.3390/ijms22115755. This article has 29 citations and is from a poor quality or predatory journal.

  5. (dziadkowiak2024muskmyastheniagravis—potential pages 13-14): Edyta Dziadkowiak, Dagmara Baczyńska, and Marta Waliszewska-Prosół. Musk myasthenia gravis—potential pathomechanisms and treatment directed against specific targets. Cells, 13:556, Mar 2024. URL: https://doi.org/10.3390/cells13060556, doi:10.3390/cells13060556. This article has 10 citations and is from a poor quality or predatory journal.

  6. (huda2023inflammationandautoimmune pages 1-2): Ruksana Huda. Inflammation and autoimmune myasthenia gravis. Frontiers in Immunology, Jan 2023. URL: https://doi.org/10.3389/fimmu.2023.1110499, doi:10.3389/fimmu.2023.1110499. This article has 49 citations and is from a peer-reviewed journal.

  7. (kaminski2024myastheniagravisthe pages 10-10): Henry J. Kaminski, Patricia Sikorski, S. Isabel Coronel, and Linda L. Kusner. Myasthenia gravis: the future is here. Journal of Clinical Investigation, Jun 2024. URL: https://doi.org/10.1172/jci179742, doi:10.1172/jci179742. This article has 70 citations and is from a highest quality peer-reviewed journal.