Effect of high mobility group box 1 on Toll-like receptor 9 in B cells in myeloperoxidase-ANCA-associated vasculitis. (2nd January 2020)

• Record Type: Journal Article
• Authors: Wang, Chen; Deng, Hui; Gong, Yan; You, Ran; Chen, Min; Zhao, Ming-Hui
• Is Part Of: Autoimmunity. Volume 53:Number 1(2020)
• Page Start: 28
• Page End: 34
• Publication Date: 2020-01-02
• Subjects: High mobility group box 1 -- Toll-like receptor 9 -- antineutrophil cytoplasmic antibody-associated vasculitis -- B cell -- cell proliferation; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; 571.973
• DOI: 10.1080/08916934.2019.1696777
• Languages: English
• ISSNs: 0891-6934

Abstract

Abstract: High mobility group box 1 (HMGB1) played pathogenic role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Recent findings demonstrated that Toll-like receptor 9 (TLR9) was involved in B cell tolerance breaking of autoimmune disease, including AAV. Here, we investigated the effect of HMGB1 on TLR9 in B cells of AAV. In the present work, patients with myeloperoxidase (MPO)-AAV in active stage were recruited. Intracellular TLR9 expression in various B cell subpopulations of the whole blood was detected by flow cytometry and the correlation with clinical data was analysed. Our results showed that intracellular TLR9 expression in B cells, memory B cells and plasmablasts correlated with erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). In particular, TLR9 expression in plasma cells correlated with ESR, CRP, serum creatinine, eGFR, and Birmingham Vasculitis Activity Score. To further explore the effect of HMGB1 on B cell, peripheral blood mononuclear cells (PBMCs) from AAV patients were isolated. After stimulated with HMGB1, TLR9 expression in various B cell subpopulations and proliferation ratio of live B cells were analysed by flow cytometry. We found that TLR9 expression in plasma cells and the proliferation ratio of live B cells by HMGB1 stimulation were significantly upregulated compared with the control group. Therefore, TLR9 expression in plasma cells was associated with disease activity of MPO-AAV. HMGB1 could enhance TLR9 expression in plasma cells and B cell proliferation. These indicated a role of HMGB1 on TLR9 in B cells in MPO-AAV, which would provide potential clues for intervention strategies.