Epic: Autoimmune Diseases Curation Project

[cmungall]

Overview

Comprehensive curation of autoimmune diseases for the dismech knowledge base, covering diverse autoimmune mechanisms including organ-specific, systemic, and autoinflammatory conditions.

Progress

• Existing (enhancement): 9/10 (90%)
• New diseases: 20/20 (100%) ✅
• Evidence enhancement: 20/20 (100%) ✅

Remaining Work

• Antiphospholipid Syndrome (89.8% compliance - needs review)

Key Autoimmune Mechanisms Covered

1. Antibody-mediated (anti-AChR in MG, anti-dsDNA in SLE)
2. T cell-mediated (MS, T1D)
3. Immune complex deposition
4. Complement activation
5. Cytokine dysregulation
6. Molecular mimicry
7. Epitope spreading

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Tracking issue for projects/autoimmune-diseases.md

[github-actions]

Epic Summary: Autoimmune Diseases Curation Project

This epic tracks a comprehensive curation effort covering 34 autoimmune diseases in the dismech knowledge base, spanning diverse autoimmune mechanisms and organ systems.

Current Status

Overall Progress: 29/30 diseases complete (97%)

• ✅ New diseases: 20/20 (100%) - All completed with 153 total evidence items added
• ✅ Existing disease enhancements: 9/10 (90%) - Enhanced with new evidence and improved compliance
• ⚠️ Remaining work: 1 disease needs review

Remaining Work

Antiphospholipid Syndrome (89.8% compliance - needs review)

• Current status: High compliance score but marked for review
• File: kb/disorders/Antiphospholipid_Syndrome.yaml
• Contains: 6 pathophysiology entries, 12 phenotypes, 4 biochemical markers, 2 genetic markers, 2 environmental factors
• Evidence: Extensively documented with 71 evidence items across all sections
• Possible review items:
  • HLA-DR7 genetic marker has 3 NO_EVIDENCE items (lines 751-777)
  • HLA-DR4 marked as negative but has REFUTE evidence suggesting association (lines 778-793)
  • Smoking environmental factor has empty evidence array (line 797)
  • Some evidence items marked as PARTIAL or NO_EVIDENCE may need updating

Diseases Successfully Curated

New Diseases Added (20)

Systemic Autoimmune:

• Sjögren's Syndrome (9 evidence items)
• Systemic Sclerosis (6 evidence items)
• Mixed Connective Tissue Disease (9 evidence items)
• Dermatomyositis (12 evidence items)
• Polymyositis (11 evidence items)

Neurological:

• Myasthenia Gravis (9 evidence items)
• Guillain-Barré Syndrome (7 evidence items)
• Chronic Inflammatory Demyelinating Polyneuropathy (6 evidence items)

Musculoskeletal:

• Ankylosing Spondylitis (9 evidence items)

Hepatobiliary:

• Primary Biliary Cholangitis (9 evidence items)
• Autoimmune Hepatitis (6 evidence items)
• Primary Sclerosing Cholangitis (7 evidence items)

Vasculitis:

• Giant Cell Arteritis (9 evidence items)
• Granulomatosis with Polyangiitis (10 evidence items)
• Behçet's Disease (6 evidence items)

Dermatological:

• Pemphigus Vulgaris (7 evidence items)
• Alopecia Areata (10 evidence items)

Hematological:

• Autoimmune Hemolytic Anemia (7 evidence items)
• Immune Thrombocytopenia (7 evidence items)

Renal:

• IgA Nephropathy (7 evidence items)

Enhanced Existing Diseases (9)

• Stiff Person Syndrome: 100% compliance ✅
• Multiple Sclerosis: 86.6% → 92.0% (added IL7R, IL2RA evidence)
• Rheumatoid Arthritis: 83.0% → 87.6% (added JAK/STAT, PADI4 evidence)
• Vitiligo: 80.0% → 86.7% (added IFIH1, BACH2, IRF4, FOXP3 evidence)
• Graves' Disease: 77.7% → 81.9% (added CTLA4, PTPN22, CD40, TSHR evidence)
• Systemic Lupus Erythematosus: 77.6% → 79.4% (added Anifrolumab, Belimumab evidence)
• Addison's Disease: 73.4% → 77.7% (added CYP21A2, HLA, CTLA4, PTPN22 evidence)
• Crohn's Disease: 75.2% → 76.2% (added autophagy/Paneth cell evidence)
• Type 1 Diabetes: 53.7% → 60.2% (added interferon, HLA-DQ2, PTPN22, IL2RA, CTLA4, Teplizumab, CGM evidence)

Autoimmune Mechanisms Documented

The project successfully covers 7 major autoimmune mechanisms:

1. Antibody-mediated - Autoantibodies targeting self-antigens (e.g., anti-AChR in Myasthenia Gravis, anti-dsDNA in SLE)
2. T cell-mediated - Autoreactive T cells attacking tissues (e.g., Multiple Sclerosis, Type 1 Diabetes)
3. Immune complex deposition - Circulating immune complexes causing tissue damage
4. Complement activation - Complement-mediated tissue destruction
5. Cytokine dysregulation - Aberrant inflammatory cytokine production
6. Molecular mimicry - Cross-reactivity between pathogen and self-antigens
7. Epitope spreading - Expansion of autoimmune response to additional self-antigens

Common Autoantibodies Documented

• ANA (antinuclear antibodies)
• Anti-dsDNA
• Anti-Ro/SSA, Anti-La/SSB
• ANCA (anti-neutrophil cytoplasmic antibodies)
• Anti-CCP (anti-cyclic citrullinated peptide)
• Anti-TPO, Anti-thyroglobutin
• Anti-AChR (acetylcholine receptor)
• Anti-GAD65

Quality Metrics

• All files pass schema validation ✅
• All files pass term validation ✅
• All files pass reference validation ✅
• Compliance range: 60-100% (with weighted scoring at 66-100%)
• Total evidence items added: 153+ across new diseases

Next Steps

To complete this epic:

1. Review Antiphospholipid Syndrome file for:
   • Empty evidence arrays (smoking environmental factor)
   • Genetic markers with NO_EVIDENCE or conflicting evidence
   • Consider removing or updating entries that lack supporting evidence
2. Run final QC: just qc
3. Close epic once Antiphospholipid Syndrome reaches satisfactory state

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Note: This represents a substantial contribution to the dismech knowledge base, adding 20 new autoimmune diseases and significantly enhancing 9 existing entries with evidence-based pathophysiology, phenotypes, and treatment information.