Increased levels of chemokine receptor CXCR3 and chemokines IP-10 and MIG in patients with primary biliary cirrhosis and their first degree relatives

Ya Hui Chuang, Zhe Xiong Lian, Chun Mei Cheng, Ruth Y. Lan, Guo Xiang Yang, Yuki Moritoki, Bor Luen Chiang, Aftab A. Ansari, Koichi Tsuneyama, Ross L. Coppel, M. Eric Gershwin

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Infiltrating memory T cells play an important role in the destruction of the biliary tract in primary biliary cirrhosis (PBC) and inflammatory chemokines control lymphocyte traffic through their interactions with T cell chemokine receptors. In the present study, we measured plasma levels of chemokines interferon-γ-inducible protein-10 (IP-10) and monokine induced by gamma interferon (MIG), and also studied the expression of CXCR3 chemokine receptors in 105 subjects, including 53 patients with PBC, 26 first degree relatives and 26 healthy controls. Interestingly, plasma IP-10 and MIG levels in PBC were increased significantly compared to controls and appeared to increase with disease progression. By immunohistochemistry, IP-10 and MIG expressions were evident in the portal areas in PBC. Further, the frequency of CXCR3-expressing cells in peripheral blood was also significantly higher in PBC, and CXCR3-positive cells were also found in the portal areas of diseased livers, primarily on CD4+ cells. Finally, the daughters and sisters of PBC patients also demonstrated increased plasma levels of IP-10 and MIG, but, in contrast, displayed normal frequency of CXCR3+ expressing peripheral blood lymphocytes. Our data imply a role for specific chemokine-chemokine receptor interactions in the pathogenesis of PBC and also highlight the familial risk factor.

Original languageEnglish (US)
Pages (from-to)126-132
Number of pages7
JournalJournal of Autoimmunity
Volume25
Issue number2
DOIs
StatePublished - Sep 2005

Keywords

  • CXCR3
  • Interferon-γ-inducible protein-10 (IP-10)
  • Monokine induced by gamma interferon (MIG)
  • Primary biliary cirrhosis (PBC)

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Chuang, Y. H., Lian, Z. X., Cheng, C. M., Lan, R. Y., Yang, G. X., Moritoki, Y., Chiang, B. L., Ansari, A. A., Tsuneyama, K., Coppel, R. L., & Gershwin, M. E. (2005). Increased levels of chemokine receptor CXCR3 and chemokines IP-10 and MIG in patients with primary biliary cirrhosis and their first degree relatives. Journal of Autoimmunity, 25(2), 126-132. https://doi.org/10.1016/j.jaut.2005.08.009