Recent advances support the concept of IgG4-related disease as a unique systemic disease, because autoimmune pancreatitis, sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis show similar pathological features with an abundant infiltration of IgG4 positive plasma cells and fibrosis, and steroid responsive. Based on these findings, a novel concept of IgG4-related disease such as IgG4-related systemic sclerosing disease, IgG4-systemic plasmacytic syndrome (SIPS), and IgG4-related multiorgan lymphoproliferative disease (IgG4-MOLPS) have been proposed. However, pathogenetic mechanisms still remain unclear. For clarifying it, genetic background, humoral immunity, complement system, disease-related antibodies, cellular immunity, and regulatory T cells were reviewed. Although the significance of IgG4 in the development of IgG4-related disease still remains unclear, we have proposed a hypothesis for the pathogenesis in AIP, one of IgG4-related diseases. In induction of lesions, the initial response to selfantigens or molecular mimicry for components of H. pylori may be induced by decreased naive-Tregs, and Th1 cells release proinflammatory cytokines. In progression, increased memory-Tregs and Th2 immune responses regulate IgG4 production. Further studies are necessary to clarify the pathogenesis.
Keywords: IgG, IgG4-related disease, autoimmune pancreatitis, Mikulicz's disease, regulatory T cell (Treg), sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis, multiorgan lymphoproliferative disease, lachrymal glands, Carbonic anhydrase-II, Cytotoxic T lymphocyte antigen-4, Plasminogen-binding protein, Ubiquitin-protein ligase E3 component n- recognin 2, Systemic lupus erythematosus