title: Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases.
abstract: OBJECTIVE
  Patients with autoimmune pancreatitis (AIP) characteristically show elevated serum levels of immunoglobulin G4 (IgG4) and abundant infiltration of IgG4-positive plasmacytes in the involved organs. The most common involved organ showing extrapancreatic lesions is the bile duct, which exhibits sclerosing cholangitis (SC). However, the role of IgG4 in the development of IgG4-related SC (IgG4-SC) remains unclear. To clarify the role of IgG4 in IgG4-SC, we have performed an immunohistochemical analysis of the bile duct.
  
  
  METHODS
  Laboratory and immunohistochemical findings of liver biopsy specimens obtained from patients with IgG4-SC, primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and primary biliary cirrhosis (PBC) were compared. The biopsy specimens were first stained with anti-IgG1, anti-IgG4, and anti-Foxp3 (forkhead box P3) antibodies, and the ratio of IgG4-, IgG1-, and Foxp3-positive cells, respectively, to infiltrated mononuclear cells (IgG4/Mono, IgG1/Mono, Foxp3/Mono) was assessed.
  
  
  RESULTS
  The ratio of IgG4/IgG1-positive plasma cells was significantly higher in specimens obtained from patients with IgG4-SC than in those from patients with PSC, AIH, and PBC. The Foxp3/Mono ratio in patients with PBC was significantly higher than that in patients with IgG4-SC and PSC. In patients with IgG4-SC, the number of Foxp3-positive cells was significantly correlated with the number of IgG4-positive cells; in the other patient groups, there was no correlation.
  
  
  CONCLUSIONS
  The IgG4/IgG1 ratio in the liver may be a useful marker for differential diagnosis of IgG4-SC and PSC. In IgG4-SC, abundant infiltration of regulatory T cells (Tregs) may affect the switching of B cells to IgG4-producing plasmacytes, and there is a possibility that the function of Tregs is different in IgG4-SC and other liver diseases (PSC, AIH, and PBC).
authors.affiliation: Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono, Moriguchi, Osaka, 570-8507, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Koyabu
authors.forename: Kazushige
authors.initials: K
authors.lastname: Uchida
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Yutaku
authors.initials: Y
authors.lastname: Sakaguchi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fukui
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ikeda
authors.forename: Makoto
authors.initials: M
authors.lastname: Takaoka
authors.forename: Junko
authors.initials: J
authors.lastname: Hirohara
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishio
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Uemura
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology; D001652:Bile Ducts / Q000276:immunology; D001706:Biopsy; D015209:Cholangitis, Sclerosing / Q000175:diagnosis / Q000276:immunology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007150:Immunohistochemistry; D008105:Liver Cirrhosis, Biliary / Q000276:immunology; D008107:Liver Diseases / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G