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Increased circulating PD-1hiCXCR5- peripheral T helper cells are associated with disease activity of ANCA-associated vasculitis.

Newly identified PD-1hiCXCR5-CD4+ T-cells, termed as peripheral helper T-cells (Tph), have been found elevated and playing a pathogenic role in some autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatic arthritis (RA). However, the potential role of Tph-cells in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains unclear. Here, we explored the potential clinical significance of circulating Tph-cells in the pathogenesis of AAV. Comparing 32 active AAV patients and 18 age- and sex-matched healthy controls (HCs), we found that the frequency of circulating Tph-cells was significantly expanded in active AAV patients. Besides, programmed death 1 (PD-1) expression on the surface of Tph-cells was significantly up-regulated in active AAV patients. Importantly, the frequency of circulating Tph-cells was greatly decreased in AAV patients after receiving treatment. Tph-cells frequency was positively correlated with the Birmingham Vasculitis Activity Score (BVAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil lymphocyte ratio (NLR), and cellular crescent in active AAV patients, but negatively correlated with fibrosus crescent. Tph-cells frequency was also positively correlated with naïve B-cells, serum concentration of MPO-ANCAs, serum tumor necrosis factor-α (TNF-α), IL-4, IL-21, and IL-12. However, serum IL-10 exhibited a negative correlation with circulating Tph-cells in active AAV patients. These results demonstrate that circulating Tph-cells are greatly expanded in active AAV patients and are positively associated with serum MPO-ANCAs and disease activity, thus contributing to the pathogenesis of AAV.