Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases.
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).
Koyabu
Masanori
M
Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono, Moriguchi, Osaka, 570-8507, Japan.
Uchida
Kazushige
K
Miyoshi
Hideaki
H
Sakaguchi
Yutaku
Y
Fukui
Toshiro
T
Ikeda
Hiroki
H
Takaoka
Makoto
M
Hirohara
Junko
J
Nishio
Akiyoshi
A
Uemura
Yoshiko
Y
Uemoto
Shinji
S
Okazaki
Kazuichi
K
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
D007074:Immunoglobulin G