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.