title: Autoimmune pancreatitis--a new evolving pancreatic disease?
abstract: BACKGROUND
  Recent advances support the concept of autoimmune pancreatitis as a unique systemic disease because occasional extrapancreatic lesions such as sclerosing cholangitis, sclerosing sialoadenitis, and retroperitoneal fibrosis show similar pathological features with fibrosis and abundant infiltration of IgG4-positive plasma cells, and are steroid responsive. Based on these findings, several diagnostic criteria have been proposed.
  
  
  METHODS
  Although AIP is accepted worldwide as a unique clinical entity, pathogenetic mechanism still remains unclear. To clarify it, genetic background, humoral immunity, candidates of target antigens including self-antigens and molecular mimicry from microbes, cellular immunity including regulatory T cells, complement system, and experimental models are reviewed.
  
  
  RESULTS
  Based on these findings, we have proposed a hypothesis for the pathogenesis of AIP in the biphasic mechanism of "induction" and "progression." In the early stage, initial response to self-antigens (LF, CA-II, CA-IV, PSTI, or α-fodrin) or molecular mimicry (Helicobacter pylori) is induced by decreased naive regulatory T cells (Tregs), and Th1 cells release proinflammatory cytokines (IFN-γ, IL-1b, IL-2, and TNF-α).
  
  
  CONCLUSIONS
  In the chronic stage, progression is supported by increased memory Tregs and Th2 immune responses. The classical pathway of complement system may be activated by IgG1 immune complex.
  
  
  CONCLUSIONS
  As Tregs seem to take important roles in progression as well as induction of the disease, further studies are necessary to clarify the pathogenesis.
authors.affiliation: The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Shinmachi, Hirakata, Osaka, 573-1197, Japan. okazaki@hirakata.kmu.ac.jp
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
authors.forename: Kazushige
authors.initials: K
authors.lastname: Uchida
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fukui
authors.forename: Makoto
authors.initials: M
authors.lastname: Takaoka
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishio
mesh_terms: D000465:Algorithms; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007125:Immunogenetics; D007074:Immunoglobulin G / Q000032:analysis; D018836:Inflammation Mediators / Q000502:physiology; D018716:Molecular Mimicry / Q000276:immunology; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010950:Plasma Cells / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D001324:Autoantigens; D007074:Immunoglobulin G; D018836:Inflammation Mediators