title: Ursodeoxycholic acid reduces CpG-induced IgM production in patients with primary biliary cirrhosis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Fourth Department of Internal Medicine, Teikyo University Mizonokuchi Hospital, Kawasake, Kangawa, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Willy
authors.initials: W
authors.lastname: Hsu
authors.forename: Naomi
authors.initials: N
authors.lastname: Hosoya
authors.forename: Yuki
authors.initials: Y
authors.lastname: Moritoki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kajiyama
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kawai
authors.forename: Atsuko
authors.initials: A
authors.lastname: Takai
authors.forename: Eriko
authors.initials: E
authors.lastname: Hayami
authors.forename: Carlo
authors.initials: C
authors.lastname: Selmi
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyakawa