title: Identification of commensal flora-associated antigen as a pathogenetic factor of autoimmune pancreatitis.
abstract: OBJECTIVE
  Autoimmune pancreatitis (AIP) is a chronic fibro-inflammatory disease of the pancreas constituting, in part, a recently defined nosological entity of IgG4-related systemic sclerosing diseases. The pathogenetic factors of AIP have not been fully elucidated. We previously established a mouse model of AIP using chronic exposure to a commensal bacteria, Escherichia coli.
  
  
  METHODS
  To determine the pathogenetically relevant antigen of E. coli, the outer membrane fractions of E. coli were subjected to two-dimensional gel electrophoresis followed by immunoblotting against sera from the AIP model. Immunoreactive spots were determined using MALDI TOF/MS and Mascot search. The recombinant protein of the identified antigen was examined for their ability to induce AIP-like disorder in C57BL/6 mice. Furthermore, the antibody titer against that antigen was determined in AIP patients.
  
  
  RESULTS
  One representative spot reacting with sera from E. coli-inoculated mice was identified as FliC from E. coli, based on the results of TOF/MS. The repeated inoculation of recombinant FliC in C57BL/6 mice induced AIP-like pancreatitis and higher titers of anti-lactoferrin and anti-carbonic anhydrase II. Sera from patients with AIP had the highest antibody titer, while those from patients with pancreatic diseases other than AIP had a higher antibody titer against E. coli and FliC, compared with pancreatic disease-free controls.
  
  
  CONCLUSIONS
  FliC from E. coli may pathogenetically generate an AIP-like inflammation status. A reconsideration of the importance of commensal bacteria as an environmental factor(s) capable of inducing autoimmunity could provide insight to overcoming AIP.
authors.affiliation: Department of Microbiology and Immunology, Tokyo Women's Medical University, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Yanagisawa
authors.affiliation: Department of Microbiology and Immunology, Tokyo Women's Medical University, Japan; Department of Gastroenterology and Medicine, Tokyo Women's Medical University, Japan. Electronic address: haruta@research.twmu.ac.jp.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Haruta
authors.affiliation: Department of Gastroenterology and Medicine, Tokyo Women's Medical University, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: Department of Microbiology and Immunology, Tokyo Women's Medical University, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Higuchi
authors.affiliation: Department of Pathology, Tokyo Women's Medical University, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Shibata
authors.affiliation: Department of Gastroenterology and Medicine, Tokyo Women's Medical University, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shiratori
authors.affiliation: Department of Microbiology and Immunology, Tokyo Women's Medical University, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yagi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008969:Molecular Sequence Data; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification
chemical_list: D000942:Antigens, Bacterial; D001323:Autoantibodies; D001425:Bacterial Outer Membrane Proteins; D011994:Recombinant Proteins
keywords: Autoantibody; Autoimmune pancreatitis (AIP); Commensal bacteria; FliC of Escherichia coli; Innate immunity