Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver-kidney transplantation

Background/Aims: Liver allograft is known to protect simultaneously transplanted organs from acute rejection. We have reported that only 6% of combined liver-kidney recipients, versus 32.5% of kidney recipients, develop kidney graft acute rejection. Release of soluble human leukocyte antigen (HLA) molecules by the liver has been proposed as a possible tolerogenic mechanism involved in the better acceptance of double transplants. The HLA-G molecule is acknowledged to possess tolerogenic properties. Methods: We investigated the involvement of HLA-G in allogeneic transplant acceptance by analyzing its expression in kidney and liver biopsies of 40 combined transplanted patients. Results: We demonstrate the presence of HLA-G in 14 out of 40 liver and five out of nine kidney transplants biopsies. HLA-G is expressed de novo by cells that are otherwise frequently susceptible target cells of acute rejection, i.e. liver biliary and renal tubular epithelial cells. We show a significant association between HLA-G expression in liver biliary epithelial cells and the absence of liver graft rejection. No acute or chronic rejection of the kidney graft was observed in patients in whom HLA-G was expressed in the liver graft. Conclusions: HLA-G expression in the liver allograft is associated with a lower frequency of hepatic and renal acute rejection and may be involved in the acceptance of simultaneously transplanted organs. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.