Authors: Kazuichi Okazaki Kazushige Uchida Toshiro Fukui
Publish Date: 2008/07/04
Volume: 43, Issue: 6, Pages: 409-
Abstract
Recent advances support the concept of autoimmune pancreatitis AIP as a unique systemic disease because it shows occasional extrapancreatic lesions such as sclerosing cholangitis sclerosing sialoadenitis and retroperitoneal fibrosis pathological features similar to those of fibrosis and abundant infiltration of IgG4positive plasma cells and it is steroid responsive Based on these findings several diagnostic criteria have been proposed Although AIP is accepted worldwide as a unique clinical entity its pathogenetic mechanism remains unclear To clarify its pathogenesis its genetic background humoral immunity candidate target antigens including selfantigens and molecular mimicry by microbes and cellular immunity including regulatory T cells the complement system and experimental models are reviewed On the basis of this review we hypothesize that the pathogenesis of AIP involves a biphasic mechanism consisting of “induction” and “progression” In the early stage the initial response to selfantigens lactoferrin carbonic anhydrase CAII CAIV pancreatic secretory trypsin inhibitor and αfodrin and molecular mimicry Helicobacter pylori are induced by decreased naïve regulatory T cells Tregs and Thelper Th 1 cells release proinflammatory cytokines interferonγ interleukin IL1β IL2 and tumor necrosis factor α In the chronic stage progression is supported by increased memory Tregs and Th2 immune responses The classical complement system pathway may be activated by the IgG1 immune complex As Tregs seem to play an important role in progression as well as in induction of the disease further studies are necessary to clarify the pathogenesis of AIP
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