Background/Purpose:  In the pathogenesis of rheumatoid arthritis (RA), T cells can differentiate into functionally distinct subsets, leading to the persistent inflammation and immune abnormality associated with the interactive activation between B cells, monocytes and dendritic cells. However, little is known about pathological immune cell subsets targeted by biologic DMARDs (bDMARD) therapy. The aim of this study was to assess the therapeutic effects of bDMARDs on the diversity of immune cell phenotypes in peripheral blood of patients with RA.

Methods:  Peripheral immune cell phenotypes were determined in 108 patients with bio-naïve RA who showed inadequate response to DMARDs and 26 healthy control (HC) subjects by comprehensive 8-color flow cytometric analysis for human immune system termed “the Human Immunology Project” by NIH and FOCIS. We also examined the correlation between the phenotypes and clinical course and assessed the effects of 24-week treatment with bDMARDs.

Results: The proportions of CD3⁺CD4⁺CD45RA^–CCR7^– effector memory, CD3⁺CD4⁺CD45RA⁺CCR7^– effector T helper cells and CD4⁺CXCR5⁺ICOS⁺ T follicular helper cells (Tfh) were higher in patients with active RA than in HC. The percentages of memory T cells, CD3⁺CD4⁺CXCR3^–CCR6⁺ Th17 cells and Tfh cells correlated with serum levels of autoantibodies, whereas that of CD19⁺CD20^–CD27⁺CD38⁺ plasmablasts correlated with disease activity scores. All of bDMARDs markedly improved the disease activity scores after 24 week treatment. Treatment with TNF inhibitors reduced the proportion of CD3^–CD19^–CD14^–CD20^–HLA-DR⁺CD123⁺ plasmacytoid dendritic cells, while tocilizumab reduced the proportion of CD19⁺CD20⁺IgD^–CD27^– double-negative B cells but increased CD4⁺CCR4⁺CD25⁺CD127^lowTreg cells. Abatacept treatment resulted in marked decrease in the proportion of activated Tfh and the absolute number of Tfh, but slightly reduced Th17 and Treg cells. The proportion of Tfh cells was an independent and significant predictor of the response to abatacept therapy.

Conclusion: These results indicated that the abnormal T cell differentiation correlated with autoantibody production while plasmablast did with disease activity of RA. Molecular targeted therapies induced different changes in different immune cell phenotypes. Among the phenotypes, Tfh cells seem a potential target for abatacept. Immunophenotypic analysis is useful for evaluation of the pathogenesis and prediction of the response to bDMARDs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/abatacept-targets-t-follicular-helper-cells-in-patients-with-rheumatoid-arthritis/