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Increased Expression of PAD4 in Neutrophils of MPO-ANCA Associated Vasculitis and its Correlation with the Vasculitis Activity


      Myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitis (MPO-AAV) is the most common ANCA associated vasculitis (AAV) in china and other East Asian countries. Its pathogenesis remained elusive. We evaluated the expression of peptidylarginine deiminase (PAD4) in neutrophils from MPO-AAV and explored the relationship between the expression and the vasculitis activity, and also investigated the pathogenic mechanism. 40 patients initially diagnosed with MPO-AAV in the active state and 40 comparable healthy controls (HC) were enrolled in this study. The patient disease activity were evaluated with Birmingham Vasculitis Activity Index version 3 (BVAS-V3). The expression of PAD4 in their neutrophils, which was described as percentage of PAD4+ neutrophils in all neutrophils and mean fluorescence intensity (MFI) of PAD4+ neutrophils, was measured by flow cytometry (FCM). Their serum level of NETs, C5a and MPO-ANCA were detected using enzyme linked immunosorbent assay (ELISA). The percentage of PAD4+ neutrophils, MFI of PAD4+ neutrophils, the levels of serum NETs and C5a were markedly higher in patient group than that in HC group. Meanwhile, in patient group, the percentage of PAD4+ neutrophils, MFI of PAD4+ neutrophils and MPO-ANCA presented significantly correlation with NETs. Although univariable analysis showed the percentage of PAD4+ neutrophils, MFI of PAD4+ neutrophils, NETs, C5a and MPO-ANCA had respective correlation with BVAS, multivariable analysis indicated that only the percentage of PAD4+ neutrophils as well as the level of serious MPO-ANCA owned independent correlations with BVAS.PAD4 might be a new potential target for MPO-AAV treatment in the future.