AUTHOR=Takeda Sayo , Watanabe-Kusunoki Kanako , Nakazawa Daigo , Kusunoki Yoshihiro , Nishio Saori , Atsumi Tatsuya 

TITLE=The Pathogenicity of BPI-ANCA in a Patient With Systemic Vasculitis

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01334

DOI=10.3389/fimmu.2019.01334

ISSN=1664-3224

ABSTRACT=<p><bold>Objective:</bold> ANCA associated vasculitis (AAV) is characterized by systemic necrotizing vasculitis with the presence of ANCA. Although BPI-ANCA is one of the atypical ANCAs and is occasionally seen in patients with vasculitis, the pathogenicity of BPI-ANCA remains unclear. This study was performed to examine the pathogenic role of BPI-ANCA against neutrophils.</p><p><bold>Methods:</bold> A 76-year-old Japanese man showed BPI-ANCA positive systemic vasculitis with a medical history of <italic>Pseudomonas aeruginosa</italic> infection. BPI-ANCA IgGs were eluted from the patient serum using an immunoadsorbent column. <italic>In vitro</italic> experiment, healthy donor neutrophils were treated with BPI-AAV IgGs, MPO-AAV IgGs, healthy control IgGs under TNFα stimulation. After 3 h incubation, neutrophil extracellular trap (NET) was assessed by immunofluorescent imaging. To determine the pathogenicity of BPI-ANCA, TNFα-primed neutrophils were incubated with monoclonal BPI-ANCA in the presence or absence of recombinant BPI.</p><p><bold>Results:</bold> BPI-AAV IgGs-treated neutrophils showed NET formation with histone citrullination. Interestingly, the monoclonal BPI-ANCA did not induce NET, but the immune complexes (ICs) of recombinant BPI and BPI-ANCA induced TNFα-dependent NET formation with hypercitrullination. Furthermore, TNFα increased the expression of BPIs in neutrophils and the BPIs were translocated to cell surface.</p><p><bold>Conclusion:</bold> BPI-ANCA could affect neutrophils leading to NET formation and may play a role in the development of systemic vasculitis as pathogenic autoantibody.</p>