Identification of commensal flora-associated antigen as a pathogenetic factor of autoimmune pancreatitis

Naoko Yanagisawa, Ikuko Haruta, Kyoko Shimizu, Toru Furukawa, Tomoaki Higuchi, Noriyuki Shibata, Keiko Shiratori, Junji Yagi

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objectives: 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.

Original languageEnglish
Pages (from-to)100-106
Number of pages7
JournalPancreatology
Volume14
Issue number2
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Keywords

  • Autoantibody
  • Autoimmune pancreatitis (AIP)
  • Commensal bacteria
  • FliC of Escherichia coli
  • Innate immunity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Gastroenterology

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  • Cite this

    Yanagisawa, N., Haruta, I., Shimizu, K., Furukawa, T., Higuchi, T., Shibata, N., Shiratori, K., & Yagi, J. (2014). Identification of commensal flora-associated antigen as a pathogenetic factor of autoimmune pancreatitis. Pancreatology, 14(2), 100-106. https://doi.org/10.1016/j.pan.2014.01.004