Session Title: Rheumamtoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovium, causing progressive joint destruction and reduction in quality of life for patients. The treatment of RA is largely based on management of the clinical consequences and manifestation of joint inflammation, which is likely to be remote from the fundamental pathophysiologic defects. Identification of cellular subsets or biomarkers that differentiate distinct clinic features according to the pathophysiologic defects is a necessary first step toward making a more accurate prognosis and better therapeutic decisions. Here, we identify a novel T cell subset, follicular helper T cells (Tfh) in RA patients and examine the hypothesis that Tfh cells may participate in the pathogenesis in RA by fostering an environment for self-reactive B cells, resulting in autoantibody production.
Peripheral blood was collected from 20 RA patients meeting 2010 ACR/EULAR RA classification criteria and age/gender matched healthy donors. Synovial fluid specimens from actively inflamed joints of RA patients were also collected. Clinical disease activity was quantified using the Disease Activity Score in 28 joints (DAS-28). RA patients were divided into remission, mild/moderate, and severe groups based on their DAS-28 score. Serum laboratory measurements including Rheumatoid factor, anti-cyclic citrullinated peptide, Erythrocyte sedimentation rate and C Reactive Protein levels were obtained. Tonsil specimens were obtained from discarded surgical tissue of non-RA patients and used as positive controls. Surface phenotype (CXCR5, CD57, ICOS, PD-1, BTLA) and intracellular cytokine (IL-21) production were used to identify Tfh cells in RA peripheral blood, RA synovial fluid, and normal tonsil by flow cytometry and/or immunohistochemical staining. Surface phenotype CD20 and CD38 were used to identify plasmablasts. IgG production was measured by ELISA from the co-culture of autologous B cells with their respective tonsillar Tfh cells, or RA peripheral blood Tfh and non-Tfh cells.
A novel T cell subset with Tfh cell surface molecule and signature cytokine was identified in both of the peripheral blood and the synovial fluid from RA patients. The percentage of these Tfh-like cells was expanded in the peripheral blood and synovial fluid of active RA patients (DAS-28 > 2.6) (P<0.05), compared to healthy donors and RA patients in remission (DAS-28 <2.6). The percentage of Tfh-like cells in CD4+ T cells of the peripheral blood of RA patients correlated with the percentage of plasmablasts in the total lymphocyte population, and also with the level of pathogenic auto-antibody (anti-CCP) and DAS-28. IgG levels were significantly increased in co-culture of Tfh-like cells and peripheral blood B cells of RA patients, but not in co-culture of non-Tfh-like cells and RA peripheral B cells.
Identification of an expanded population of Tfh-like cells in RA patients provides evidence that a distinctive germinal center pathway maybe involved in RA pathogenesis resulting in autoimmunity. Targeting RA-Tfh-like cells may provide more precise treatment strategies.
J. M. Zakem,
W. E. Davis,
T. A. Webb-Detiege,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-follicular-helper-t-cells-as-a-novel-cell-population-potentially-involved-in-the-pathogenesis-of-rheumatoid-arthritis/