title: IgG4-associated cholangitis.
abstract: IgG4-associated cholangitis (IAC) is the hepatobiliary manifestation of immunoglobulin G4-related disease (IgG4-RD), a systemic fibroinflammatory disorder with a wide variety of clinical presentations and organ manifestations. IgG4-RD predominantly affects the hepatobiliary tract (IAC) and pancreas (autoimmune pancreatitis) and mimics hepatobiliary, pancreatic and other malignancies. Patients typically are 60-80 years old and 80-85% are male. They often present with painless obstructive jaundice and organ swelling that can be mistaken for pancreatic or bile duct cancer, as well as primary or secondary sclerosing cholangitis. An accurate diagnostic marker is lacking and extensive surgery for presumed malignant hepatobiliary or pancreatic disease leads to the diagnosis of IgG4-RD in 1 of 3 patients. Early effective immunosuppressive treatment is often missed. The pathogenesis of IgG4-RD has been enigmatic. We recently identified dominant IgG4+ B-cell receptor clones in blood and tissue of patients with IAC, but not in healthy or disease controls, and hypothesized that specific B-cell responses are pivotal to the pathogenesis of IAC and IgG4-RD. Analysis of our Amsterdam cohort and blinded extramural validation of the Oxford cohort of patients with IgG4-RD disclosed a remarkable association with 'blue-collar work'. Thus, long-term exposure to solvents and other organic agents might predispose to IgG4-RD.
authors.affiliation: Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
authors.forename: Lucas J
authors.initials: LJ
authors.lastname: Maillette de Buy Wenniger
authors.forename: Marieke
authors.initials: M
authors.lastname: Doorenspleet
authors.forename: Lowiek
authors.initials: L
authors.lastname: Hubers
authors.forename: Joanne
authors.initials: J
authors.lastname: Verheij
authors.forename: Thomas
authors.initials: T
authors.lastname: van Gulik
authors.forename: Stan F J
authors.initials: SF
authors.lastname: van de Graaf
authors.forename: Niek
authors.initials: N
authors.lastname: de Vries
mesh_terms: D002761:Cholangitis / Q000175:diagnosis / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G