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