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