Increased Th17 cell activity in patients with early rheumatoid and psoriatic arthritis (137.30)

Abstract

Abstract To gain insights into the role of Th17 cells in human autoimmune diseases, we analyzed Th17 cell biology in patients with ongoing inflammatory autoimmune arthritis (e.g., rheumatoid (RA) and psoriatic arthritis (PsA)), and for control in patients with osteoarthritis and healthy individuals. Frequencies of Th17 cells were significantly elevated in the blood of patients with early, treatment-naive RA and PsA. Moreover, upon activation in vitro, CD4 T cells from the patients yielded enhanced Th17 frequencies and elevated levels of IL-17. In contrast, Th1 frequencies and IFNγ production were not different between patients and controls. As the frequencies of Th17 cells and IL-17 production, but not of Th1 cells or IFNγ production correlated with disease activity, early inflammation in RA and PsA is characterized by both, selectively enhanced Th17 cell generation and increased Th17 cell activity. Of interest for the pathogenesis of autoimmune arthritis, CD4 T cells from early RA and PsA patients were partially resistant to the inhibitory capacity of IL-4 and IFNγ on Th17 generation, suggesting a potential mechanism underlying the breakdown of peripheral tolerance at disease onset. However, as effective immunosuppressive treatment was associated with normalization of Th17 cell activity in the patients, the data further suggest that Th17 cells might also contribute to sustained autoimmune inflammation in RA and PsA.