Autoimmune pancreatitis--a new evolving pancreatic disease?
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.
Okazaki
Kazuichi
K
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
Uchida
Kazushige
K
Fukui
Toshiro
T
Takaoka
Makoto
M
Nishio
Akiyoshi
A
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
D000936:Antigen-Antibody Complex; D001324:Autoantigens; D007074:Immunoglobulin G; D018836:Inflammation Mediators