The relationship between hepatic immunoglobulin production and CD154 expression in chronic liver diseases.
BACKGROUND
CD40-CD154 is a receptor-ligand pair that provides key communication signals between cells of the adaptive immune system in states of inflammation and autoimmunity. The CD40 receptor is expressed constitutively on B lymphocytes, for which it provides important signals regulating clonal expansion and antibody production. CD154 is a member of the tumor necrosis factor superfamily, which is primarily expressed by activated T cells.


METHODS
Because many chronic liver diseases are characterized by lymphocytic infiltration of the liver and several have increased immunoglobulin (Ig) production, the role of CD40-CD154 in hepatic Ig production was investigated in patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis, autoimmune hepatitis (AIH), hepatitis C, hepatitis B, alcoholic and non-alcoholic steatohepatitis, as well as normal controls.


RESULTS
Soluble CD154 levels in the serum were found to be no different in chronic liver diseases vs normal controls. Likewise, CD154 mRNA levels in peripheral blood mononuclear cells did not differ. However, mRNA for CD154 was significantly increased in the liver of individuals with PBC and AIH as compared with the other groups. The quantity of CD154 mRNA in the liver correlated positively with the quantity of mRNA for secretory Ig.


CONCLUSIONS
These findings suggest that CD40-CD154 signals may be involved in Ig production within the liver of autoimmune liver diseases.
Mayo
Marlyn J
MJ
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9151, USA. marlyn.mayo@utsouthwestern.edu
Mosby
James M
JM
Jeyarajah
Rohan
R
Combes
Burton
B
Khilnani
Smina
S
Al-halimi
Maha
M
Handem
Iorna
I
Grammer
Amrie C
AC
Lipsky
Peter E
PE
D023201:CD40 Ligand / Q000097:blood* / Q000235:genetics; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000235:genetics; D007075:Immunoglobulin M / Q000097:blood* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012333:RNA, Messenger; D023201:CD40 Ligand