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Induction of proteinase 3-anti-neutrophil cytoplasmic autoantibodies by proteinase 3-homologous bacterial protease in mice.

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Authors
Kim, Yong Chul; Choi, Yun Sik; Alam, Jehan; Kim, Yun-Ji; Baek, Keum Jin; Koh, Jaemoon; Song, Yeong Wook; Chung, Doo-Hyun; Choi, Youngnim
Issue Date
2016-03-07
Publisher
Springer
Keywords
Granulomatosis with polyangiitisHumanMousePR3AutoantibodiesSaccharomonospora viridis
Abstract
Proteinase 3 (PR3) is the principal target of antineutrophil cytoplasmic autoantibodies (ANCA) associated with granulomatosis with polyangiitis. The aim of this study was to investigate whether bacterial PR3-homologous protease can induce autoantibodies to PR3 and ANCA-associated pathology in mice. Among the bacterial proteases that have greater than 30 % identity with PR3, a trypsin-like serine protease of Saccharomonospora viridis, a bacterium that causes hypersensitivity pneumonitis, was chosen. When the mice were immunized with the recombinant protease of S. viridis (SvPR), 75 % of NZBWF1 and 100 % of C57BL/6 mice developed high levels of autoantibodies to mouse PR3 (mPR3). The levels of antibodies to mPR3 had a strong positive correlation with those to SvPR. In addition, more than half of the mPR3-reactive sera (63 %) reacted to purified human PR3 (hPR3), and the levels of antibodies to hPR3 had a positive correlation with those to mPR3. The sera from the immunized mice strongly stained murine neutrophils in a C-ANCA pattern. Although granulomatous inflammation and signs of vasculitis were observed in several mice, they were attributable to the use of complete Freunds adjuvant in the immunization. Collectively, exposure to PR3-homologous bacterial protease could induce ANCA in mice, and this finding may provide a new insight into the triggering mechanisms for the production of PR3–ANCA.
Language
English
URI
https://hdl.handle.net/10371/95633
DOI
https://doi.org/10.1007/s12026-015-8687-4
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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