Curate Myasthenia Gravis

[cmungall]

Curate kb/disorders/Myasthenia_Gravis.yaml

✅ Complete - 9 evidence items added

Part of Epic #216

[github-actions]

Summary: Myasthenia Gravis Curation

Status

✅ COMPLETED - This issue was successfully completed as part of Epic #216 (Autoimmune Diseases Curation Project)

What Was Accomplished

The Myasthenia Gravis entry (kb/disorders/Myasthenia_Gravis.yaml) was enhanced with 9 evidence items covering:

Pathophysiology Evidence (6 items)

1. Autoantibody-Mediated NMJ Dysfunction - 2 evidence items

   • PMID:37869140 - Confirms autoantibodies targeting AChR complex at NMJ
   • PMID:29266249 - Documents 74-88% prevalence of AChR autoantibodies in generalized MG

2. Complement Activation - 3 evidence items

   • PMID:29266249 (2 snippets) - MAC formation and NMJ damage mechanisms
   • PMID:37869140 - IgG1/IgG3 complement activation

3. Thymic Abnormalities - 2 evidence items

   • PMID:21922466 (2 snippets) - Thymus role in pathogenesis and autoimmunization

Subtype Evidence (2 items)

4. MuSK Antibody-Positive MG - 2 evidence items
   • PMID:21674519 (2 snippets) - Bulbar involvement, female predominance, and disease severity

Treatment Evidence (6 items)

5. Acetylcholinesterase Inhibitors - 2 evidence items

   • PMID:36184373 (2 snippets) - Patient-reported effectiveness and side effects

6. Thymectomy - 2 evidence items

   • PMID:27509100 (2 snippets) - Landmark MGTX trial showing improved outcomes

7. Eculizumab - 2 evidence items

   • PMID:29066163 (2 snippets) - REGAIN trial for refractory disease

8. Plasma Exchange - 1 evidence item

   • PMID:21674519 - Effectiveness in MuSK-MG

Entry Quality Highlights

The curated entry demonstrates strong adherence to dismech standards:

✅ Comprehensive subtyping: 5 well-defined subtypes (AChR+, MuSK+, Seronegative, Ocular, Thymoma-associated)

✅ Mechanistic depth: 3 pathophysiology mechanisms with proper ontology bindings:

• GO:0007274 (neuromuscular synaptic transmission)
• GO:0006956 (complement activation)
• CL:0002293 (epithelial cell of thymus)

✅ Clinical phenotypes: 7 phenotypes with HPO terms, including diagnostic markers (muscle weakness, ptosis, fatigability)

✅ Treatment diversity: 9 treatments spanning symptomatic (AChE inhibitors), immunosuppressive, surgical, and novel biologics (complement inhibitors)

✅ MAXO treatment terms: Properly annotated with Medical Action Ontology including:

• MAXO:0000645 (acetylcholinesterase inhibitor therapy)
• MAXO:0001483 (complement 5 inhibitor agent therapy)
• MAXO:0001079 (thymectomy)

Context: Epic #216 Progress

This issue was part of the larger Autoimmune Diseases Curation Project:

• Overall epic progress: 29/30 diseases complete (96.7%)
• Remaining work: Only Antiphospholipid Syndrome (Enhance Antiphospholipid Syndrome #217) needs review
• Key autoimmune mechanisms covered: Antibody-mediated, T cell-mediated, complement activation, molecular mimicry

Scientific Notes

Myasthenia Gravis serves as an excellent example of antibody-mediated autoimmunity with several notable features:

1. Prototypic neuromuscular junction disorder: Well-characterized autoantibodies (anti-AChR, anti-MuSK) with direct functional consequences

2. Complement-dependent pathology: Unlike some autoimmune diseases, MG pathogenesis requires MAC formation for NMJ damage (confirmed in animal models)

3. Therapeutic evolution: The entry captures the progression from symptomatic treatment (AChE inhibitors) → immunosuppression → biologics (eculizumab, the first complement inhibitor approved for neuromuscular disease)

4. Thymic involvement: Central role of thymus in pathogenesis makes thymectomy an effective disease-modifying intervention (MGTX trial PMID:27509100)

Potential Future Enhancements

While this entry is comprehensive, future curators might consider:

• Additional complement inhibitors (ravulizumab, zilucoplan) as they gain approval
• FcRn inhibitors (efgartigimod, rozanolixizumab) - newer therapeutic class
• Clinical trial annotations for ongoing studies
• Genetic associations beyond HLA (CTLA4, PTPN22, etc.)

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This automated summary was generated to enhance issue tracking and knowledge retention for the dismech project.