| Domain | Core entity/finding | Suggested ontology identifiers/terms | Evidence/interpretive note |
|---|---|---|---|
| Disease identity | Adult-onset autoimmune myasthenia gravis | MONDO: MONDO_0018324; parent disease MONDO_0009688 myasthenia gravis; ICD-10: G70.0 | Adult-onset MG is an antibody-mediated autoimmune neuromuscular junction disease; age-, antibody-, thymus-, and trigger-based subgroups are clinically meaningful (pqac-00000023, pqac-00000025) |
| Classification | Autoimmune, acquired, postsynaptic neuromuscular junction disorder | MeSH: Myasthenia Gravis; category: autoimmune disease; not congenital myasthenic syndrome | Guideline and review distinguish autoimmune MG from congenital myasthenic syndromes; routine knowledge base entry should treat adult-onset MG as acquired disease-level knowledge, not single-patient EHR-derived only (pqac-00000024, pqac-00000025) |
| Synonyms | Adult-onset MG; late-onset MG subset when onset ≥50 years; generalized MG / ocular MG as phenotypic forms | Labels only: adult-onset myasthenia gravis; autoimmune myasthenia gravis | Early- vs late-onset and ocular vs generalized are clinically useful sub-stratifications rather than strict synonyms (pqac-00000022, pqac-00000013) |
| Core autoantibody endotypes | AChR-MG, MuSK-MG, LRP4-MG, seronegative MG | AChR antibody positive; MuSK antibody positive; LRP4 antibody positive; seronegative MG | About 80% of generalized MG and ~50% of ocular MG have AChR antibodies; MuSK antibodies occur in 5%–8% of AChR-negative patients; LRP4 is less common (pqac-00000023, pqac-00000005) |
| Phenotype | Fluctuating fatigable weakness | HPO: Muscle weakness; Fatigability | Hallmark symptom complex used diagnostically and in severity scoring (pqac-00000023, pqac-00000024) |
| Phenotype | Ptosis | HPO: Ptosis | Common ocular presentation; ocular MG defined by ptosis/diplopia-limited disease (pqac-00000023, pqac-00000013) |
| Phenotype | Diplopia | HPO: Diplopia | Core ocular manifestation and frequent presenting feature (pqac-00000023) |
| Phenotype | Bulbar weakness/dysphagia/dysarthria | HPO: Dysphagia; Dysarthria; Bulbar palsy | Especially prominent in MuSK-MG and severe generalized disease (pqac-00000004, pqac-00000023) |
| Phenotype | Respiratory insufficiency / myasthenic crisis | HPO: Respiratory insufficiency; Acute respiratory failure | Life-threatening generalized phenotype; crises incorporated into active/refractory disease definitions (pqac-00000023, pqac-00000024) |
| Phenotype | Generalized limb/axial weakness | HPO: Proximal muscle weakness; Generalized weakness | Generalized MG may involve ocular, bulbar, axial, limb, and respiratory muscles (pqac-00000023, pqac-00000025) |
| Burden/QoL | Persistent fatigue and reduced quality of life | MG-ADL; QMG; MG-QoL15r; EQ-5D-5L | Fatigue can persist even in pharmacologic remission and is associated with lower QoL/depressive symptoms (pqac-00000026, pqac-00000025) |
| Anatomy | Primary anatomical site: neuromuscular junction | UBERON: neuromuscular junction; synapse; skeletal muscle | Disease mechanism centers on the postsynaptic muscle membrane of the NMJ (pqac-00000023, pqac-00000022) |
| Anatomy | Postsynaptic membrane / motor end plate | UBERON labels: motor end plate; postsynaptic membrane | AChR loss, fold simplification, and MAC injury are localized here (pqac-00000022) |
| Anatomy | Thymus involvement in major subgroups | UBERON: thymus | Thymic hyperplasia and thymoma are relevant in AChR-MG; MuSK-MG generally lacks prominent thymic involvement; all patients should be imaged for thymoma (pqac-00000025, pqac-00000004) |
| Cell types | Autoreactive B cells / plasmablasts / plasma cells | CL: B cell; plasmablast; plasma cell | B-cell activation and autoantibody production are central upstream mechanisms; rituximab responsiveness supports B-cell contribution (pqac-00000004, pqac-00000003) |
| Cell types | CD4+ T cells / T follicular helper-like support | CL: T cell; CD4-positive, alpha-beta T cell | MG is T-cell-dependent and antibody-mediated; tolerance failure and T-cell help sustain pathogenic antibodies (pqac-00000023) |
| Cell types | Thymic epithelial cells | CL label: thymic epithelial cell | Aberrant thymic biology contributes particularly to AChR-MG and thymoma-associated MG (pqac-00000003, pqac-00000015) |
| Mechanism | Complement-mediated postsynaptic injury in AChR-MG | GO: complement activation; membrane attack complex assembly | AChR IgG1/IgG3 antibodies activate complement, causing MAC-mediated injury and fold loss; rationale for C5 inhibitors (pqac-00000022, pqac-00000025) |
| Mechanism | Antigenic modulation/internalization of AChR | GO: receptor-mediated endocytosis; acetylcholine receptor clustering | Cross-linking promotes AChR endocytosis/degradation, reducing receptor density (pqac-00000022) |
| Mechanism | Functional block of ACh binding | GO label: chemical synaptic transmission; acetylcholine receptor activity | Some antibodies directly block AChR function at the binding site (pqac-00000022) |
| Mechanism | MuSK-LRP4 signaling disruption | GO labels: receptor signaling pathway; neuromuscular junction development; acetylcholine receptor clustering | MuSK IgG4 antibodies interfere with LRP4-MuSK interaction and impair AChR clustering rather than complement fixation (pqac-00000004) |
| Mechanism | FcRn-mediated IgG recycling sustains pathogenic antibodies | Target: FCGRT; GO label: IgG receptor activity / immunoglobulin recycling | FcRn antagonists reduce circulating IgG including pathogenic autoantibodies (pqac-00000025, pqac-00000000) |
| Mechanism | Impaired neuromuscular transmission | GO: synaptic transmission, cholinergic; muscle contraction | Final common downstream pathway explaining fatigable weakness and decremental physiology (pqac-00000022, pqac-00000023) |
| Genetics: susceptibility, not monogenic cause | HLA region risk differs by onset subgroup | HLA-DQA1; HLA-DRB1; HLA-B; HLA-A | HLA is the dominant susceptibility region; onset-specific architecture differs between early- and late-onset disease (pqac-00000010, pqac-00000015) |
| Genetics: susceptibility, not monogenic cause | TNFRSF11A risk locus | HGNC: TNFRSF11A | Replicated MG susceptibility locus; not a monogenic cause of acquired adult-onset MG (pqac-00000010, pqac-00000015) |
| Genetics: susceptibility, not monogenic cause | PTPN22 risk variant (adult-onset association evidence) | HGNC: PTPN22 | Open Targets associates PTPN22 with adult-onset MG; LOMG GWAS found suggestive rs2476601/R620W association (pqac-00000000, pqac-00000015) |
| Genetics: susceptibility, not monogenic cause | CTLA4, TNIP1, CHRNA1, AGRN | HGNC: CTLA4; TNIP1; CHRNA1; AGRN | These genes shape susceptibility architecture/endotypes; AGRN is biologically notable because it encodes an NMJ organizer, but this is still susceptibility rather than direct Mendelian causation for adult autoimmune MG (pqac-00000007, pqac-00000010) |
| Genetics: causal distinction | Adult-onset autoimmune MG is generally not caused by germline pathogenic variants in AChR-clustering genes | Distinguish from congenital myasthenic syndrome genes: CHRNE, RAPSN, DOK7, MUSK, LRP4, AGRN, COLQ, CHAT | These genes are causal in congenital myasthenic syndromes, not typical adult-onset autoimmune MG; important differential annotation in knowledge bases (pqac-00000000, pqac-00000025) |
| Environment / triggers | Infection, especially SARS-CoV-2, may trigger onset/exacerbation in some cases | Labels only: viral infection; SARS-CoV-2 infection | Epidemiologic and case-based evidence suggests possible triggering, but causality remains uncertain (pqac-00000013) |
| Environment / triggers | Immune checkpoint inhibitor-induced MG | Label: checkpoint inhibitor-induced myasthenia gravis | Recognized distinct severe-onset subgroup in modern oncology practice (pqac-00000023) |
| Environment / triggers | Medication-related worsening | Labels only: magnesium; selected antibiotics; immune therapies | Guideline/trial eligibility language warns that concurrent medications can worsen weakness; some therapies can induce or unmask MG (pqac-00000018, pqac-00000008) |
| Diagnostics | Diagnostic framework | History of fluctuating fatigable weakness + autoantibodies and/or electrophysiology and/or pharmacologic testing | Guideline-based confirmation pathway; thymic CT/MRI recommended for all patients to evaluate thymoma (pqac-00000024, pqac-00000025) |
| Diagnostics | Electrodiagnostic confirmation in seronegative disease | Repetitive nerve stimulation; single-fiber EMG | In patients without positive serology, repetitive stimulation and single-fiber testing confirm diagnosis in ~90% (pqac-00000023) |
| Biomarkers | Serologic biomarkers | AChR antibody; MuSK antibody; LRP4 antibody; total IgG | Core diagnostic and treatment-stratifying biomarkers; total IgG often tracked in FcRn-therapy trials (pqac-00000023, pqac-00000018) |
| Omics | Predictive metabolomic signature for steroid response | Histidine; free fatty acid (13:0); γ-cholestenol; guanosine | Discovery study from MGTX biospecimens found an AUC of 0.90 for a responder panel; promising but not routine clinical practice yet (pqac-00000016) |
| Standard symptomatic treatment | Pyridostigmine (acetylcholinesterase inhibitor) | NCIT label: Pyridostigmine Bromide; target/class: ACHE inhibitor | First-line symptomatic treatment for most MG; may be less useful or problematic in MuSK-MG (pqac-00000024, pqac-00000004) |
| Standard immunotherapy | Corticosteroids | NCIT label: Prednisone / glucocorticoid therapy | Foundational disease-modifying therapy for mild/moderate to active disease (pqac-00000024, pqac-00000027) |
| Steroid-sparing immunotherapy | Azathioprine, MMF, tacrolimus, cyclosporine, methotrexate | NCIT labels; classes: antimetabolite, calcineurin inhibitor, antimetabolite antifolate | Used as conventional long-term immunotherapies; azathioprine is the most established standard steroid-sparing agent in guidelines (pqac-00000027) |
| Rescue / crisis therapy | IVIG, plasmapheresis, immunoadsorption | NCIT labels: Immune Globulin; Plasma Exchange | Recommended for impending/manifest myasthenic crisis and severe exacerbation (pqac-00000024) |
| Surgery | Thymectomy for AChR-positive generalized MG and thymoma-associated MG | NCIT label: Thymectomy | MGTX showed better QMG, lower prednisone exposure, less azathioprine use, and fewer hospitalizations versus prednisone alone in nonthymomatous AChR-positive generalized MG (pqac-00000017, pqac-00000025) |
| Targeted biologic | Eculizumab / ravulizumab / zilucoplan | Target: C5; class: complement inhibitor | Best mechanistic fit for AChR-positive complement-mediated MG; guideline recommends in highly active AChR-positive generalized MG (pqac-00000025, pqac-00000009) |
| Targeted biologic | Efgartigimod / rozanolixizumab | Target: FCGRT/FcRn; class: FcRn modulator/antagonist | FcRn blockade lowers pathogenic IgG broadly; major 2023-2024 therapeutic advance with strong trial activity and approvals (pqac-00000025, pqac-00000014, pqac-00000018) |
| Targeted biologic | Rituximab | Target: CD20; class: B-cell depletion therapy | Particularly effective in MuSK-MG and considered in seronegative/LRP4-positive/highly active disease (pqac-00000024, pqac-00000004) |
| Recent trial signal | Rozanolixizumab in MuSK-positive generalized MG | FcRn inhibitor; MuSK-specific subgroup efficacy | In MycarinG MuSK subgroup, MG-ADL improved versus placebo without serious TEAEs or deaths in the subgroup analysis (pqac-00000014) |
| Active clinical development | Inebilizumab | Target: CD19; class: B-cell depletion therapy | Phase 3 MINT includes AChR- and MuSK-antibody-positive adults; reflects continued B-cell-targeted development (pqac-00000019) |
| Active clinical development | KYV-101 / mivocabtagene autoleucel | Target/class: anti-CD19 CAR-T cell therapy | Phase 2/3 trial in generalized MG after failure of multiple immunosuppressive/immunomodulatory therapies (pqac-00000021) |
| Active clinical development | NMD670 | Class: skeletal muscle ClC-1 chloride channel inhibitor / neuromuscular function enhancer | Phase 2b symptom-focused therapy in AChR/MuSK-positive MG (pqac-00000020) |
| Prevention / care considerations | Vaccination review, avoidance of precipitants, medication reconciliation | Labels only: vaccination assessment; trigger avoidance | Guideline recommends checking vaccination history before prolonged immunotherapy; tertiary prevention focuses on avoiding crises and treatment complications (pqac-00000027) |


*Table: This table summarizes knowledge-base-ready entities for adult-onset autoimmune myasthenia gravis, including disease identifiers, phenotypes, anatomy, mechanisms, susceptibility genes versus non-causal CMS genes, and treatment targets/classes. It is designed to support ontology mapping and evidence-linked curation.*