Analysis of CXCR5+Th17 cells in relation to disease activity and TNF inhibitor therapy in Rheumatoid Arthritis

Th17 and TfH cells are thought to promote tissue inflammation and autoantibody production, respectively, in autoimmune diseases including rheumatoid arthritis (RA). TfH cells that co-express Th17 markers (CXCR5⁺Th17) encompass both of these pathogenic functions, and are increased in some human autoimmune settings including juvenile dermatomyositis. We investigated CXCR5⁺Th17 cells in RA subjects with stable or active disease and before and after TNF inhibitor therapy. CXCR5⁺Th17 cell frequency was increased in RA compared to healthy controls, but other helper T cell subsets were not different. CXCR5⁺Th17 cells correlated with disease activity in subjects with active RA prior to initiation of TNF inhibitor therapy. Baseline CXCR5⁺Th17 cells also correlated with numbers of swollen joints as late as one year post-therapy. CXCR5⁺Th17 cell frequencies were unaltered by TNF blockade and in fact remained remarkably stable within individuals. We conclude that CXCR5⁺Th17 cells are not a direct target of TNF blockade and therefore cannot serve as a biomarker of current disease activity. However, basal CXCR5⁺Th17 cell frequency may indicate underlying differences in disease phenotype between patients and predict ultimate success of TNF inhibitor therapy.