Consensus gene modules strategy identifies candidate blood-based biomarkers for primary Sjögren's disease

Area of Science:

• Immunology
• Genomics
• Translational Medicine

Background:

• Primary Sjögren disease (pSD) is an autoimmune disorder affecting exocrine glands, with unclear pathophysiology and limited effective treatments.
• Understanding pSD heterogeneity is crucial for developing targeted therapies.

Purpose of the Study:

• To identify Consensus gene Modules (CMs) from whole blood transcriptomic data in pSD patients.
• To correlate these CMs with cell types, biological functions, and patient stratifications.
• To assess CMs as predictors of treatment response in a clinical trial.

Main Methods:

• Unsupervised gene classification across four datasets to identify CMs.
• Gene set enrichment analysis and transcriptomic profiling of sorted blood cells for CM annotation.
• Flow cytometry for validation of cell type abundance correlations.
• Analysis of CM expression in relation to treatment response (hydroxychloroquine and leflunomide).

Main Results:

• Thirteen distinct CMs were identified and annotated to cell types and biological functions.
• CMs successfully reconciled previous pSD patient stratifications.
• Pre-treatment expression of lymphocyte and erythrocyte modules predicted response to combination therapy.

Conclusions:

• Consensus gene modules provide a framework for understanding pSD heterogeneity.
• These CMs can serve as a basis for developing blood-based predictive biomarkers.
• This approach facilitates personalized treatment strategies for primary Sjögren disease.