| Domain | Key facts for knowledge base | Suggested ontology terms | Evidence boundaries / notes |
|---|---|---|---|
| Identity / ontology | Inclusion body myositis (IBM), often specified as sporadic inclusion body myositis (sIBM), is an acquired idiopathic inflammatory myopathy of older adults with slowly progressive, asymmetric weakness, especially of deep finger flexors and quadriceps; MONDO identifier supported in retrieved evidence: **MONDO:0007827**; hereditary inclusion-body myopathies are distinct entities and should not be merged with sIBM (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000004, pqac-00000022) | MONDO:0007827; MeSH/ICD/Orphanet: not established in retrieved evidence; distinguish from GNE myopathy, VCP-related inclusion body myopathy, MYH2- and LAMA2-related hereditary IBM forms (pqac-00000022) | Do **not** infer unsupported OMIM/Orphanet/ICD identifiers from this evidence set; Open Targets association list includes GNE/MYH2/ACVR2B but does not establish causality for sporadic IBM (pqac-00000004) |
| Phenotype / natural history | Typical phenotype: painless, asymmetric, slowly progressive weakness affecting quadriceps, deep finger flexors, and often foot extensors; common falls and dysphagia; atypical presentations can include isolated dysphagia, asymptomatic hyper-CKemia, foot drop, axial weakness, and facial/bulbar involvement. Most patients lose ambulation or become wheelchair dependent about **10–15 years** after onset; dysphagia is frequent and worsens quality of life (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000016) | HPO suggestions: muscle weakness, quadriceps weakness, finger flexor weakness, dysphagia, falls, foot drop, muscle atrophy, reduced hand grip, impaired ambulation | Precise HPO IDs were not provided in retrieved evidence; frequency estimates vary by cohort and diagnostic criteria (pqac-00000000, pqac-00000001) |
| Etiology / genetics | Etiology remains unresolved and appears multifactorial, integrating immune, degenerative, mitochondrial, and aging-related mechanisms. Genetic susceptibility is linked mainly to the **HLA/MHC region**; reported associated alleles include **HLA-DRB1*03:01, *01:01, *13:01** and possibly **CCR5**. Rare variants reported in some IBM cohorts include **VCP, SQSTM1, FYCO1**, but these do not establish monogenic causation for sporadic IBM (pqac-00000008, pqac-00000022) | Gene symbols: HLA-DRB1, CCR5, VCP, SQSTM1, FYCO1; disease distinction terms: hereditary inclusion-body myopathy, GNE myopathy | No firmly established protective genetic or environmental factors were identified in retrieved evidence. Evidence for infectious/environmental triggers is suggestive rather than causal; associations with HIV and hepatitis C support shared immune-exhaustion pathways, not proven causation (pqac-00000007) |
| Pathology / mechanisms | Core pathology combines **endomysial CD8+ T-cell inflammation**, invasion of non-necrotic **MHC-I–expressing** fibers, rimmed vacuoles, protein aggregates (**p62/SQSTM1, TDP-43, LC3, amyloid-related material**), mitochondrial abnormalities, ER stress, oxidative/nitrative stress, and impaired autophagy/proteasome function. IFN-γ-driven immune activation is prominent. Recent advanced-technology studies show: selective loss of **type 2 myonuclei/type 2A fibers**, increased **cytotoxic T cells** and **cDC1**, myofiber stress programs (**GADD45A, NORAD**), protein degradation program (**RNF7**), IBM-specific **ACHE** upregulation suggesting functional denervation, and senescent **fibro-adipogenic progenitors (FAPs)** with loss of **collagen XV** and SASP-like features. Mitochondrial DNA abnormalities and metabolic disarrangements are prominent (pqac-00000005, pqac-00000006, pqac-00000007, pqac-00000008, pqac-00000009, pqac-00000018, pqac-00000019, pqac-00000020) | GO suggestions: antigen processing and presentation, interferon-gamma signaling, autophagy, proteasomal protein catabolism, mitochondrial organization, oxidative stress response, cellular senescence, complement activation; CL suggestions: CD8-positive alpha-beta T cell, conventional dendritic cell 1, fibro-adipogenic progenitor, skeletal muscle fiber | Causal ordering remains debated: some evidence argues autoimmunity is upstream of degeneration, but refractoriness to immunosuppression and strong cell-autonomous/mitochondrial findings indicate mixed mechanisms (pqac-00000005, pqac-00000006, pqac-00000020) |
| Diagnostics | Diagnosis is clinicopathologic and multimodal: characteristic weakness pattern plus muscle biopsy, CK, EMG, MRI, and supportive serology. Anti-cN1A antibodies have reported **specificity ~90–95%** but variable **sensitivity ~37–76%**. Biopsy features include endomysial inflammation, rimmed vacuoles, T-cell invasion of non-necrotic fibers, ragged-red/COX-negative fibers, p62/TDP-43-positive inclusions, and sometimes tubulofilaments. ENMC-style criteria are emphasized in reviews; MRI and EMG support but are not standalone diagnostic tests (pqac-00000011, pqac-00000012, pqac-00000016) | Diagnostic feature suggestions: muscle biopsy finding, electromyography abnormality, creatine kinase increased, anti-cN1A antibody positive, muscle MRI abnormality | Exact ENMC text, CK ranges, MRI pattern details, and differential-diagnosis algorithms were not fully extractable from retrieved evidence. Genetic testing is mainly useful to exclude hereditary IBM mimics rather than confirm sporadic IBM (pqac-00000012, pqac-00000022) |
| Epidemiology / prognosis | IBM is the most prevalent inflammatory myopathy of older adults / most common acquired myopathy in people >50 years in cited reviews. Reported prevalence varies widely by geography and case ascertainment: about **5–180 per million** in reviews; among those ≥50 years, estimates cited include **1–182 per million**. Male predominance is roughly **2:1**. Mean age at onset is around **60 years**. Mortality is modestly increased; major causes of death include **aspiration pneumonia** and respiratory complications. Early-onset IBM is rare and severe: in one Swedish population-based study prevalence was **1.2 per million** and incidence **0.12 per million/year**, with median onset age **36** and median survival from diagnosis **14 years** (pqac-00000000, pqac-00000001, pqac-00000002) | Epidemiology annotations: prevalence, incidence, male sex predominance, adult onset, late onset | Prevalence/incidence vary greatly with criteria and whether age-restricted denominators are used. Early-onset IBM should be represented separately from classic late-onset sIBM (pqac-00000002) |
| Current care | No approved disease-modifying pharmacotherapy is established in retrieved evidence. Real-world management is supportive: monitor swallowing and respiratory status, annual dysphagia screening/history, speech-language pathology referral, adaptive food consistencies/volumes, mobility aids, exercise/physical therapy, and fall prevention. IVIG may give **temporary dysphagia benefit** in selected patients but does not clearly alter overall disease course. Cricopharyngeal dilation or myotomy may help obstructive dysphagia; botulinum toxin has case-series support. Conventional immunosuppressants are generally ineffective (pqac-00000000, pqac-00000016, pqac-00000017) | MAXO-style action suggestions: swallow evaluation, speech therapy, physical therapy, exercise therapy, mobility aid provision, respiratory monitoring, intravenous immunoglobulin administration, cricopharyngeal myotomy, endoscopic dilation | Prevention is mainly **tertiary**: reduce falls, aspiration, malnutrition, and respiratory complications. No evidence-supported primary prevention, population screening, or vaccine strategy was identified (pqac-00000016, pqac-00000017) |
| Experimental therapies | Key interventional programs from retrieved evidence: **sirolimus** (mTOR inhibition/autophagy; phase 3 **NCT04789070**, active-not-recruiting, target enrollment 140; earlier phase 2b missed primary quadriceps endpoint but showed some secondary functional signals), **ABC008 / ulviprubart** (anti-KLRG1 cytotoxic T-cell depletion; phase 1 **NCT04659031** completed; phase 2/3 **NCT05721573** completed, enrollment 272), **arimoclomol** (heat-shock response/proteostasis; large randomized trial **NCT02753530**, publication not directly retrieved here but summarized in review literature as not practice-changing), **bimagrumab** (ACVR2B/myostatin pathway; **NCT01925209**, **NCT02573467**, failed primary 6MWT endpoint despite lean-mass effects), **phenylbutyrate** (**NCT04421677**), blood-flow restricted exercise (**NCT02317094**), adipose-derived regenerative/cell therapies (**NCT04975841**, **NCT05032131**), and withdrawn REGN2477+REGN1033 (**NCT03710941**) (pqac-00000013, pqac-00000014, pqac-00000016, pqac-00000017) | Trial/target suggestions: ACVR2B, KLRG1, mTOR signaling, heat-shock response, autophagy modulation, cell therapy | Many trials remain negative, incomplete, or unpublished in full within retrieved evidence. No therapy can yet be described as established standard disease-modifying care for sporadic IBM (pqac-00000013, pqac-00000016, pqac-00000017) |


*Table: Compact evidence table for sporadic inclusion body myositis covering identity, phenotype, mechanisms, diagnostics, prognosis, and treatments. It highlights quantitative findings, ontology suggestions, and key evidence limits without inventing unsupported identifiers.*