Increased circulating PD-1hiCXCR5− peripheral T helper cells are associated with disease activity of ANCA-associated vasculitis. (12th January 2022)

• Record Type: Journal Article
• Authors: Liu, Zhenyu; Li, Xueqin; Fan, Ningning; Wang, Hong; Xia, Wenli; Li, Wenjie; Tang, Sha; Zhou, Xinyuan; Wu, Yuzhang; Zou, Liyun; Li, Jingyi; Zhang, Jingbo
• Is Part Of: Clinical and experimental immunology. Volume 207:Number 3(2022)
• Page Start: 287
• Page End: 296
• Publication Date: 2022-01-12
• Subjects: anti-neutrophil cytoplasmic antibody -- vasculitis -- peripheral helper T-cell -- BVAS -- autoimmune disease -- B lymphocytes; Immunopathology -- Periodicals; 616.079
• DOI: 10.1093/cei/uxac002
• Languages: English
• ISSNs: 0009-9104

Abstract

Abstract: Newly identified PD-1 hi CXCR5 – 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. Abstract : The role of newly identified peripheral helper T cells (Tph) in ANCA-associated vasculitis (AAV) remains largely unknown, although they have been found elevated and playing pathogenic role in some autoimmune disease including SLE and RA. In this study, Liu et al found that Tph cells were greatly expanded in active AAV patients and decreased after treatment with methylprednisolone and cyclophosphamide, and they were positively correlated with vasculitis activity index, serum concentration of MPO-ANCA, IL-4 and IL-21. These results indicate that Tph cells may play a pathogenic role in AAV through promoting plasma cell activation possibly by secreting IL-4 and IL-21. Graphical Abstract: