Background Presence of serum anti-citrullinated protein antibodies (ACPAs) in patients with rheumatoid arthritis (RA) predicts worse disease course and a more erosive disease. In the pathogenesis of RA, inflammatory T cells play a central role. In this context, we recently found increased proportions of pathogenic peripheral CCR6+ memory T helper cells in patients with early RA compared to healthy individuals. However, it is unclear how T cell proportions are distributed between ACPA+ and ACPA- patients.
Objectives Alterations in peripheral T cell populations and their pathogenic potential were examined in ACPA+ and ACPA- patient groups.
Methods A nested matched case control study was performed including 27 ACPA+ and 27 ACPA- patients with early RA. T cell profiles (Treg, Th1, Th2, Th17, Th22 and various less well classified populations) from these ACPA+ and ACPA- patients were generated based on chemokine receptor, cytokine and transcription factor expression. Differentially present T cell populations were isolated from peripheral blood and analyzed for their pathologic potential in a co-culture system with RA derived synovial fibroblasts (RASF).
Results In comparison to ACPA- patients, ACPA+ patients have higher proportions of regulatory T cells (Treg) and CD4+ memory CCR6+ T cells. Since the CCR6+ T cell population is still a heterogeneous population, four CCR6+ T cell subpopulations were distinguished by differential expression of CXCR3 and CCR4. All four CCR6+ subpopulations shared Th17 cell characteristics such as Rorγt and CCL20 expression, but IL-17A, IL-17F, IL-22 and IFN-γ expression differed greatly between these subpopulations. However, even the population with lowest expression of these cytokines showed high pathological potential as shown by stimulating IL-1β, IL-6, IL-8, COX-2 and MMP-3 expression upon co-culture with RASF. Indeed, despite dissimilar Th17 and Th1 characteristics between the CCR6+ subpopulations, all four showed highly increased pathological potential in co-culture compared to naive and T-helper-1 cells.
Conclusions ACPA+ and ACPA- patients can be distinguished by the distribution of Treg and CCR6+ T cell subpopulations. These CCR6+ subpopulations exhibit dissimilar T-helper-17 and T-helper-1 characteristics, but all possess high pathological potential, including the population that has low IL-17A/F and IL-22 expression. These findings indicate a prominent role of CCR6+ T cells in the pathogenesis of ACPA+ patients with early RA and may contribute to the worse disease outcome in ACPA+ patients.
Disclosure of Interest : None declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.