Associations Between Rheumatoid Arthritis Clinical Factors and Synovial Cell Types and States

Area of Science:

• Immunology
• Rheumatology
• Genomics

Background:

• Rheumatoid arthritis (RA) synovium exhibits diverse cell types and states.
• Limited data correlate synovial cellular findings with patient-level clinical information.

Purpose of the Study:

• To determine associations between RA clinical factors and synovial cell types/states.
• Utilize the largest cohort with combined clinical and multicell data for RA research.

Main Methods:

• Recruited active RA patients (DMARD-naive or inadequate responders).
• Collected RA clinical factors and performed synovial biopsies.
• Employed cellular indexing of transcriptomes and epitopes sequencing (CITE-seq) to derive cell type percentages and CTAPs (e.g., EFM, TF).
• Correlated RA clinical factors with cell type percentages and CTAPs.

Main Results:

• Higher DAS28-CRP3 scores correlated with increased T cell percentages.
• Patients on methotrexate (MTX) but not biologic DMARDs (bDMARDs) showed higher B cell percentages compared to DMARD-naive patients.
• Patients on bDMARDs predominantly exhibited endothelial, fibroblast, and myeloid (EFM) cell phenotypes, with none in the T and fibroblast (TF) category.

Conclusions:

• DMARDs, more than other clinical factors, show differential associations with synovial cell phenotypes in RA.
• RA therapies may influence synovium cell type/state, potentially impacting subsequent treatment responses.