Background/Purpose: CXCR5+PD-1^hi follicular helper (Tfh) and CXCR5-PD-1^hi peripheral helper (Tph) T cells play an important role in the pathogenesis of Rheumatoid Arthritis (RA) by providing help to autoantibody secreting B cells. Whereas Tfh cells typically dwell in the germinal centers of lymphoid organs, Tph cells accumulate at inflamed tissues. An increased frequency of Tph cells and of circulating counterparts of Tfh cells have been described in the peripheral blood of patients with seropositive RA. Our objective was to examine the effect of treatment escalation using biological agents (TNF blockers or abatacept), on the frequency of circulating Tfh (cTfh) and Tph (cTph) cells in RA.

Methods: Peripheral blood was drawn from seropositive RA patients with an incomplete response to csDMARDS (n=29) who initiated biological therapy with TNF blockers (TNFb) (n= 17) or abatacept (n= 12), prescribed based on routine clinical practice. cTfh and cTph cell frequencies were determined by flow cytometry of freshly isolated PBMCs at the basal visit and 6 months after starting treatment escalation. For each patient, an age and gender-matched healthy control (HC) was also studied at both time points (n=29).

Results: As compared with HC, active RA patients receiving csDMARDs demonstrated a baseline increased frequency of both cTfh and cTph cells. A significant improvement of disease activity as determined by the DAS28 score (∆DAS28 >2.0) was apparent in all of the patients 6 months after initiating biologicals. At that time point, a significant reduction of the previously elevated cTph cell frequency was observed in both treatment groups. However, cTfh cells remained elevated in patients receiving TNFb notwithstanding a good therapeutic response, whereas subjects receiving abatacept experienced a significant abatement of their cTfh cell frequency. Experimental variation of the cTfh and cTph cell numbers in HC was minimal.

Conclusion: Abatacept but not TNFb, are able to bring down cTfh cell numbers in RA. This indicates that costimulation blockade can help attain an immunological remission, whereas TNF neutralization may allow a persistent pathogenic germinal center overactivity. At the same time, treatment with both abatacept and TNF blockers results in a downmodulation of the previouly elevated cTph cell numbers, in parallel with the remitting local joint inflammation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/differential-effect-of-abatacept-vs-tnf-blockers-on-the-frequency-of-circulating-follicular-helper-tfh-and-periperal-helper-tph-t-cells-in-rheumatoid-arthritis/