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

ABSTRACT Objective Recent studies have uncovered diverse cell types/states in the RA synovium; however limited data exist correlating these findings with patient-level clinical information. Using the largest cohort to date with clinical and multi-cell data, we determined associations between RA clinical factors with cell types/states in the RA synovium. Methods The Accelerated Medicines Partnership Rheumatoid Arthritis study recruited subjects with active RA on no DMARDs or inadequate response to methotrexate (MTX) or tumor necrosis factor inhibitors. RA clinical factors were systematically collected. Biopsies were performed on an inflamed joint and tissue disaggregated and processed with a CITE-seq pipeline from which cell type percentages and cell type abundance phenotypes (CTAP) were derived: endothelial/fibroblast/myeloid (EFM), fibroblasts (F), myeloid (M), T/B cells (TB), T cells/fibroblasts (TF), T/myeloid cells (TM). Correlations were measured between RA clinical factors, % cell type, and CTAPs. Results We studied 72 subjects, mean age 57 years, 75% female, 83% seropositive, mean RA duration 6.6 years, mean DAS28-CRP3 4.8. Higher DAS28-CRP3 correlated with higher % T cells (p<0.01). Subjects on MTX not on bDMARD had higher %B cells vs no DMARDs (p<0.01). The majority of subjects on bDMARDs were categorized as EFM (57%), while none were TF. No significant difference was observed across CTAPs for age, sex, RA disease duration, DAS28-CRP3. Conclusion In this comprehensive screen of clinical factors, we observed differential associations between DMARDs and cell phenotypes, suggesting that RA therapies, more than other clinical factors may impact cell type/state in the synovium and ultimately response to subsequent therapies.