Introduction: 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.
Materials and 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).
Discussion: 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.
Conclusion: As Tregs seem to take important roles in progression as well as induction of the disease, further studies are necessary to clarify the pathogenesis.