title: Induction of proteinase 3-anti-neutrophil cytoplasmic autoantibodies by proteinase 3-homologous bacterial protease in mice.
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 Freund's 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.
authors: Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.|KSJ Probioticslab, 4 Inchon-ro 17ga-gil, Seongbuk-gu, Seoul, Republic of Korea.
authors: Yong Chul
authors: http://orcid.org/0000-0002-6496-5560
authors: YC
authors: Kim
authors: Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors: Yun Sik
authors: YS
authors: Choi
authors: Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors: Jehan
authors: J
authors: Alam
authors: Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors: Yun-Ji
authors: YJ
authors: Kim
authors: Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
authors: Keum Jin
authors: KJ
authors: Baek
authors: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Jaemoon
authors: J
authors: Koh
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Yeong Wook
authors: YW
authors: Song
authors: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Doo-Hyun
authors: DH
authors: Chung
authors: Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea. youngnim@snu.ac.kr.
authors: Youngnim
authors: Y
authors: Choi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000096:biosynthesis* / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D006099:Granuloma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D053146:Myeloblastin / Q000737:chemistry / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins; D012697:Serine Endopeptidases / Q000737:chemistry / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D001426:Bacterial Proteins; D011994:Recombinant Proteins; C114880:trypsin-like serine protease; D012697:Serine Endopeptidases; D053146:Myeloblastin
keywords: Autoantibodies; Granulomatosis with polyangiitis; Human; Mouse; PR3; Saccharomonospora viridis