Ursodeoxycholic acid reduces CpG-induced IgM production in patients with primary biliary cirrhosis

Kentaro Kikuchi, Willy Hsu, Naomi Hosoya, Yuki Moritoki, Yusuke Kajiyama, Toshihiro Kawai, Atsuko Takai, Eriko Hayami, Carlo Selmi, M. Eric Gershwin, Hiroshi Miyakawa

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Aim: Ursodeoxycholic acid (UDCA) treatment reduces IgM serum levels in patients with primary biliary cirrhosis (PBC) without affecting serum antimitochondrial antibody (AMA) titers. We previously reported that PBC-associated hyper-IgM is secondary to a disease-specific hyperproduction following bacterial stimulation by B cells. Methods: We isolated peripheral blood mononuclear cells (PBMC) from patients with PBC and controls and evaluated whether bacterial CpG challenge in the presence of UDCA at concentrations consistent with those achieved in treated patients led to changes in total IgM, IgG-AMA, and IgM-AMA production. Further, p65 phosphorylation and CD38 cell expression were analyzed as measures of activation of the NF-kB signaling pathway and B cell subsets, respectively. Results: UDCA significantly reduced CpG-induced total IgM and IgM-AMA production, but had no impact on IgG-AMA production. UDCA also significantly reduced the activation ofnaïve and IgM memory, but not IgG memory, B cells, as represented by CD38 expression levels. Further, p65 phosphorylation was significantly reduced in the presence of UDCA. Conclusion: UDCA reduces total and IgM-AMA production in PBMC from patients with PBC by downregulating B cell activation and NF-kB signaling. These data ultimately suggest novel mechanisms of action for UDCA in chronic autoimmune cholestasis.

Original languageEnglish (US)
Pages (from-to)448-454
Number of pages7
JournalHepatology Research
Volume39
Issue number5
DOIs
StatePublished - 2009

Keywords

  • Autoantibody
  • Autoimmune cholangitis
  • Bile acids
  • Innate immunity

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

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