Curate Sjögren's Syndrome

[cmungall]

Curate kb/disorders/Sjogrens_Syndrome.yaml

✅ Complete - 9 evidence items added

Part of Epic #216

[github-actions]

Summary: Sjögren's Syndrome Curation Completed

Status: ✅ Completed with 9 evidence items added
Part of: Epic #216 (Autoimmune Diseases Curation Project)

Curation Overview

This task successfully curated kb/disorders/Sjogrens_Syndrome.yaml with comprehensive pathophysiological mechanisms, evidence-based phenotypes, and structured ontology annotations.

Key Pathophysiology Mechanisms Added (4 mechanisms, 9 evidence items)

1. Exocrine Gland Lymphocytic Infiltration (1 evidence item)

   • CD4+ T cells and B cells infiltrate salivary/lacrimal glands forming ectopic germinal center-like structures
   • Cell types: CD4+ T cells (CL:0000624), B cells (CL:0000236)
   • Evidence: PMID:33911236

2. Autoantibody Production (1 evidence item)

   • Anti-Ro/SSA and anti-La/SSB targeting ribonucleoprotein complexes
   • Driven by B-cell activation with high NHL risk
   • Evidence: PMID:38542233

3. Type I Interferon Signature (2 evidence items)

   • Elevated IFN activity via plasmacytoid dendritic cells
   • Dysregulated pathways: NF-κB, inflammasome, IFN signaling
   • Major therapeutic target in clinical trials
   • Evidence: PMID:33911236, PMID:38982205

4. Epithelial Cell Dysfunction (2 evidence items)

   • Aberrant apoptosis, antigen presentation, BAFF production
   • Bidirectional epithelium-immune cell crosstalk
   • Disease characterized as autoimmune epithelitis
   • Evidence: PMID:33911236, PMID:38982205

Phenotypes with Evidence (4 phenotypes, 3 additional evidence items)

• Xerostomia (HP:0000217) - VERY_FREQUENT - Evidence: PMID:38982205
• Keratoconjunctivitis Sicca (HP:0001097) - VERY_FREQUENT
• Arthritis (HP:0001369) - FREQUENT (non-erosive polyarthritis)
• Fatigue (HP:0012378) - VERY_FREQUENT - Evidence: PMID:38982205

Biochemical Markers (5 markers, 1 evidence item)

• Anti-Ro/SSA (60-70% in primary SS)
• Anti-La/SSB (30-40%, more specific)
• Rheumatoid Factor
• Hypergammaglobulinemia
• BAFF (elevated, promotes B-cell survival) - Evidence: PMID:38542233

Ontology Coverage

✅ Disease term: MONDO:0010030 (Sjogren syndrome)
✅ Cell types: 3 CL terms (CD4+ T cell, B cell, epithelial cell)
✅ Biological processes: 4 GO terms (adaptive immune response, immunoglobulin production, type I interferon response, apoptotic process)
✅ Phenotypes: 4 HP terms with appropriate frequency annotations

Evidence Quality

• Total evidence items: 9
• All evidence: Human clinical (HUMAN_CLINICAL)
• All snippets: Exact quotes from PubMed abstracts
• Support classification: All marked as SUPPORT
• Reference diversity: 3 unique PMIDs (33911236, 38542233, 38982205)

Scientific Rigor

The curation captures the current mechanistic understanding of Sjögren's syndrome:

• Innate immunity (type I IFN signature, epithelial dysfunction)
• Adaptive immunity (B-cell/T-cell infiltration, autoantibodies)
• Epithelium-immune crosstalk (bidirectional activation)
• Therapeutic targets (IFN pathway, B-cell activation, co-stimulation)

Integration with Epic #216

This completes one of the tasks in the Autoimmune Diseases Curation Project, which covers diverse mechanisms including:

• Antibody-mediated pathology ✅ (anti-Ro/SSA, anti-La/SSB)
• T cell-mediated pathology ✅ (CD4+ infiltration)
• Cytokine dysregulation ✅ (IFN, BAFF)

Epic status: 29/30 diseases complete (96.7%), only Antiphospholipid Syndrome remaining for review.

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Note: The disorder file passes schema validation and follows dismech best practices for evidence attribution, ontology term usage, and clinical accuracy.