Gut Liver.  2014 Sep;8(5):462-470. 10.5009/gnl14107.

Recent Advances in the Concept and Pathogenesis of IgG4-Related Disease in the Hepato-Bilio-Pancreatic System

• Okazaki K
• Yanagawa M
• Mitsuyama
• Uchida K

• KMID: 2070055
• DOI: http://doi.org/10.5009/gnl14107

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.

Keyword

IgG4-related disease; Autoimmune pancreatitis; IgG4-related sclerosing cholangitis; IgG4-related hepatopathy

MeSH Terms

Adaptive Immunity
Autoimmune Diseases/*immunology
B-Cell Activating Factor/metabolism
Cholangitis, Sclerosing/*immunology
Cholecystitis/*immunology
Humans
Immunoglobulin G/*immunology
Interleukin-10/metabolism
Liver Diseases/*immunology
Pancreatitis/*immunology
T-Lymphocytes, Regulatory/immunology
B-Cell Activating Factor
Immunoglobulin G
Interleukin-10