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Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Objectives

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).

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Acknowledgments

This work was supported in part by Health and Labour Sciences Research Grants for research on intractable diseases from Ministry of Health, Labor, and Welfare of Japan. We thank Dr. Noriko Sakaida and Dr. Chisato Ohe for their suggestions on the pathology. We also thank Dr. Daisuke Harada and Dr. Yoshihide Ueda for management of the liver samples of the PSC patients in Kyoto University Hospital. We thank Dr. Norimasa Fukata, Dr. Takeo Kusuda, Dr. Katsunori Yoshida, Dr. Tsukasa Ikeura, Dr. Yoshitsugu Nakahashi, and Dr. Mitsunobu Matsushita for excellent advice.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono, Moriguchi, Osaka, 570-8507, Japan

    Masanori Koyabu, Kazushige Uchida, Hideaki Miyoshi, Yutaku Sakaguchi, Toshiro Fukui, Hiroki Ikeda, Makoto Takaoka, Junko Hirohara, Akiyoshi Nishio & Kazuichi Okazaki

  2. Department of Clinical Sciences and Laboratory Medicine, Kansai Medical University, Moriguchi, Osaka, Japan

    Yoshiko Uemura

  3. Division of Hepato-Pancreato-Biliary Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan

    Shinji Uemoto

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  1. Masanori Koyabu
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  2. Kazushige Uchida
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  12. Kazuichi Okazaki
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Correspondence to Kazuichi Okazaki.

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Koyabu, M., Uchida, K., Miyoshi, H. et al. Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases. J Gastroenterol 45, 732–741 (2010). https://doi.org/10.1007/s00535-010-0199-3

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  • DOI: https://doi.org/10.1007/s00535-010-0199-3

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