title: Recent advances in the concept and pathogenesis of IgG4-related disease in the hepato-bilio-pancreatic system.
abstract: Recent studies have proposed nomenclatures of type 1 autoimmune pancreatitis (AIP) (IgG4-related pancreatitis), IgG4-related sclerosing cholangitis (IgG4-SC), IgG4-related cholecystitis, and IgG4-related hepatopathy as IgG4-related disease (IgG4-RD) in the hepato-bilio-pancreatic system. In IgG4-related hepatopathy, a novel concept of IgG4-related autoimmune hepatitis (AIH) with the same histopathological features as AIH has been proposed. Among organs involved in IgG4-RD, associations with pancreatic and biliary lesions are most frequently observed, supporting the novel concept of "biliary diseases with pancreatic counterparts." Targets of type 1 AIP and IgG4-SC may be periductal glands around the bile and pancreatic ducts. Based on genetic backgrounds, innate and acquired immunity, Th2-dominant immune status, regulatory T (Treg) or B cells, and complement activation via a classical pathway may be involved in the development of IgG4-RD. Although the role of IgG4 remains unclear in IgG4-RD, IgG4-production is upregulated by interleukin 10 from Treg cells and by B cell activating factor from monocytes/basophils with stimulation of toll-like receptors/nucleotide-binding oligomerization domain-like receptors. Based on these findings, we have proposed a hypothesis for the development of IgG4-RD in the hepato-bilio-pancreatic system. Further studies are necessary to clarify the pathogenic mechanism of IgG4-RD.
authors.affiliation: Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
authors.affiliation: Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Yanagawa
authors.affiliation: Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mitsuyama
authors.affiliation: Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Uchida
mesh_terms: D056704:Adaptive Immunity; D001327:Autoimmune Diseases / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000378:metabolism; D015209:Cholangitis, Sclerosing / Q000276:immunology*; D002764:Cholecystitis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D008107:Liver Diseases / Q000276:immunology*; D010195:Pancreatitis / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D016753:Interleukin-10
keywords: Autoimmune pancreatitis; IgG4-related disease; IgG4-related hepatopathy; IgG4-related sclerosing cholangitis