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

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 ALP have not been fully elucidated. We previously established a mouse model of ALP 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 ALP 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 ALP 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 ALP-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. Copyright (C) 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.