Background/Purpose:

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovium, which causes progressive joint destruction and reduction in quality of life for patients. The Th1/Th2 paradigm is a model for the induction and regulation of immune responses. Th1 cells participate in cell-mediated immunity whereas Th2 cells support humoral immunity. Recently, Tfh and Th17 cells have emerged as the novel T cell subsets controlling autoimmunity. Identifying their roles may break the Th1/Th2 axis dichotomy, bridge the knowledge gap of T cell lineages on RA immunopathogenesis, and lead to novel therapeutic approaches for RA patients. We examined the frequency of Tfh and Th17 cells in RA patients, and investigated their correlation with disease activity, autoantibody levels, and inflammation. 

Methods:

Peripheral blood was collected from 51 RA patients meeting 2010 ACR/EULAR RA classification criteria and 51 age-/gender-matched healthy donors. Clinical disease activity was quantified using the Disease Activity Score in 28 joints (DAS-28). RA patients were divided into remission (DAS-28<2.6) and active disease groups (DAS-28>2.6) based on their DAS-28. Serum laboratory measurements including Rheumatoid Factor (RF), Anti-cyclic Citrullinated Peptide antibody (anti-CCP), Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were obtained. The frequency of Tfh cells (CD4⁺CXCR5⁺ICOS⁺ PD-1⁺) and Th17 cells (CD4⁺CCR4⁺CCR6⁺) were measured by flow cytometry and analyzed by sequential gating. The plasmablasts (CD20^loCD38⁺CD138^–) in the peripheral blood were measured by flow cytometry. Correlation of the frequency of circulating Tfh cells and Th17 cells with DAS-28, plasmablasts, and laboratory parameters were statistically determined. 

Results:

Both circulating Tfh cells (CD4⁺CXCR5⁺ICOS⁺ PD-1⁺) and Th17 cells (CD4⁺CCR4⁺CCR6⁺) were significantly increased in RA patients, expecially in moderate/severe patients (p<0.05), comparing to healthy donors. The frequency of circulating Tfh cells correlated with the percentage of plasmablasts and the level of pathogenic anti-CCP antibody, whereas the frequency of circulating Th17 cells correlated with the serum level of RF and CRP as well as DAS-28. 

Conclusion:

Our data suggests that Tfh and Th17 cells may play different roles in RA pathogenesis. Tfh cells may contribute to B cell differentiation and autoantibody production,  while Th17 cells may be involved in the inflamation and pathogenesis of RA. Thus, disrupting the signals provided by Tfh and Th17 cells may offer new therapeutic stategies for severe RA patients and shift their immune system toward homeostasis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-novel-paradigm-in-the-clinical-context-of-rheumatoid-arthritis-role-of-tfh-and-th17-cells-in-autoimmunity/