Systemic sclerosis & Raynaud's
Novel human leukocyte antigen (HLA) class I and II insights into the pathogenesis of systemic sclerosis–associated interstitial lung disease
Authors' conclusion
In this study, we identify genetic mechanisms underlying SSc-ILD that support the potential implication of CD8+ T cells and ATAs in its pathogenesis.
Study context
- Population
- Patients with systemic sclerosis (SSc) with and without ILD and controls of European ancestry from 10 international cohorts10 international cohorts
- Participants
- 2,412 / 3,550 / 15,076
- Comparison
- SSc-ILD⁺ vs SSc-ILD⁻ vs controls
- SSc-ILD⁺n = 2,412
- SSc-ILD⁻n = 3,550
- Controlsn = 15,076reference
- Outcome
- Associations within HLA class I and II genes with SSc-ILD
Methodological detailsMajor histocompatibility complex (MHC)-wide association study with meta-analysis, multicohort (10 international cohorts), inverse variance weighted meta-analysis, conditional stepwise analyses, adjustment for antitopoisomerase autoantibody (ATA) status
- MHC-wide association study with meta-analysis
- Multicohort (10 international cohorts)
- Inverse variance weighted meta-analysis
- Conditional stepwise analyses
- Adjustment for ATA status
Pooled result
As reported in the abstract
- Significant associations within class I and class II HLA genes after conditional analysis
- 12
Further pooled results
Composite score (genetic, clinical, demographic variables) to predict SSc-ILD
- AUC
- 0.754
- Significantly outperformed models including any of the variables alone
Original publication
Novel HLA class I and II insights into the pathogenesis of systemic sclerosis–associated interstitial lung disease. Ann Rheum Dis. Published 30 May 2026. doi:10.
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