Circulating Tfh cells are differentially modified by abatacept or TNF blockers and predict treatment response in rheumatoid arthritis

Objective CD4(+)CXCR5(+)PD-1(hi )follicular helper T (Tfh) cells dwell in the germinal centres (GCs) of lymphoid organs and participate in RA pathogenesis. The frequency of their circulating counterparts (cTfh frequency) is expanded in RA and correlates with the pool of GC Tfh cells. Our objective was to study the effect of abatacept (ABT) or TNF blockers (TNFbs) on the cTfh frequency in RA. Methods Peripheral blood was drawn from seropositive, long-standing RA patients chronically receiving conventional synthetic DMARDs (csDMARDs; n = 45), TNFb (n = 59) or ABT (n = 34) and healthy controls (HCs; n = 137). Also, patients with an incomplete response to csDMARDs (n = 41) who initiated TNFb (n = 19) or ABT (n = 22) were studied at 0 and 12 months. The cTfh frequency was examined by cytometry. Results As compared with HCs, an increased cTfh frequency was seen in seropositive, long-standing RA patients chronically receiving csDMARDs or TNFb but not ABT. After changing from csDMARDs, the cTfh frequency did not vary in patients who were given TNFb but decreased to HC levels in those given ABT. In the ABT group, the baseline cTfh frequency was higher for patients who attained 12-month remission (12mr) vs those who remained active (12ma): 0 month cut-off for remission >0.38% [sensitivity 92%, specificity 90%, odds ratio (OR) 25.3]. Conversely, in the TNFb group, the baseline cTfh frequency was lower for 12mr vs 12ma: 0 month cut-off for non-remission >0.44% (sensitivity 67%, specificity 90%, OR 8.5). Conclusion ABT but not TNFb was able to curtail the cTfh frequency in RA. A higher baseline cTfh frequency predicts a good response to ABT but a poor response to TNFb.