Plasma cells and the chronic nonsuppurative destructive cholangitis of primary biliary cirrhosis

Toru Takahashi, Tomofumi Miura, Junichiro Nakamura, Satoshi Yamada, Tsutomu Miura, Masahiko Yanagi, Yasunobu Matsuda, Hiroyuki Usuda, Iwao Emura, Koichi Tsuneyama, Xiaosong He, M. Eric Gershwin

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

There has been increased interest in the role of B cells in the pathogenesis of primary biliary cirrhosis (PBC). Although the vast majority of patients with this disease have anti-mitochondrial antibodies, there is no correlation of anti-mitochondrial antibody titer and/or presence with disease severity. Furthermore, in murine models of PBC, it has been suggested that depletion of B cells may exacerbate biliary pathology. To address this issue, we focused on a detailed phenotypic characterization of mononuclear cell infiltrates surrounding the intrahepatic bile ducts of patients with PBC, primary sclerosing cholangitis, autoimmune hepatitis, chronic hepatitis C, and graft-versus-host disease, including CD3, CD4, CD8, CD20, CD38, and immunoglobulin classes, as well as double immunohistochemical staining for CD38 and IgM. Interestingly, CD20 B lymphocytes, which are a precursor of plasma cells, were found in scattered locations or occasionally forming follicle-like aggregations but were not noted at the proximal location of chronic nonsuppurative destructive cholangitis. In contrast, there was a unique and distinct coronal arrangement of CD38 cells around the intrahepatic ducts in PBC but not controls; the majority of such cells were considered plasma cells based on their expression of intracellular immunoglobulins, including IgM and IgG, but not IgA. Patients with PBC who manifest this unique coronal arrangement were those with significantly higher titers of anti-mitochondrial antibodies. Conclusion: These data collectively suggest a role for plasma cells in the specific destruction of intrahepatic bile ducts in PBC and confirm the increasing interest in plasma cells and autoimmunity. (HEPATOLOGY 2012)

Original languageEnglish (US)
Pages (from-to)846-855
Number of pages10
JournalHepatology
Volume55
Issue number3
DOIs
StatePublished - Mar 2012

ASJC Scopus subject areas

  • Hepatology

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    Takahashi, T., Miura, T., Nakamura, J., Yamada, S., Miura, T., Yanagi, M., Matsuda, Y., Usuda, H., Emura, I., Tsuneyama, K., He, X., & Gershwin, M. E. (2012). Plasma cells and the chronic nonsuppurative destructive cholangitis of primary biliary cirrhosis. Hepatology, 55(3), 846-855. https://doi.org/10.1002/hep.24757