Blood PD-1+TFh and CTLA-4+CD4+ T Cells Predict Remission after CTLA-4Ig Treatment in Early Rheumatoid Arthritis

Objective Treatment with CTLA-4Ig blocks T-cell activation and is clinically effective in RA. However, it is unknown if specific CD4(+) T-cell subsets in blood at baseline predict remission after CTLA-4Ig, or other biological treatments with different modes of action, and how treatment affects CD4(+) T cells in patients with untreated early RA (eRA). Methods This study included 60 patients with untreated eRA from a larger randomized trial. They were treated with methotrexate combined with CTLA-4Ig (abatacept, n = 17), anti-IL6 receptor (tocilizumab, n = 21) or anti-TNF (certolizumab-pegol, n = 22). Disease activity was assessed by clinical disease activity index (CDAI), DAS28, swollen joint counts, tender joint counts, CRP and ESR. The primary outcome was CDAI remission (CDAI <= 2.8) at week 24. Proportions of 12 CD4(+) T-cell subsets were measured by flow cytometry at baseline and after 4, 12 and 24 weeks of treatment. Results In patients treated with CTLA-4Ig, the proportions of PD-1(+)TFh and CTLA-4(+) conventional CD4(+) T cells at baseline predicted CDAI remission at week 24. CD4(+) T-cell subset proportions could not predict remission after treatment with anti-IL6R or anti-TNF. The percentage of regulatory T cells (Tregs) expressing CTLA-4 decreased in all treatment arms by 24 weeks, but only CTLA-4Ig treatment significantly reduced the proportions of Tregs and PD-1(+)T follicular helper (TFh) cells. Conclusion These findings indicate that circulating proportions PD-1(+)TFh and CTLA-4(+) conventional CD4(+) T cells at baseline may serve as predictive biomarkers for remission in early RA after CTLA-4Ig treatment.