Evolution of soluble forms of CD86, CD95 and CD95L molecules in liver transplant recipients

Co-stimulatory factors such as CD86 and apoptotic molecules such as CD95 and CD95L required to start and to turn off the allogenic immune response may also be present as soluble proteins. To determine the role of the soluble forms of CD86 (sCD86), CD95 (sCD95) and CD95L (sCD95L) in the outcome of liver transplants, we analyzed the circulating levels of these molecules in patients subjected to liver transplantation in the pre-operative period and during the first month post-transplantation. Serum samples were obtained from sixty-nine first orthotopic liver transplants (OLT). The patients were classified into acute rejection (AR=24) and not acute rejection (NAR=45), or considering the presence of chronic active hepatitis B or C (VP=30) or other primary liver diseases (VN=39). The levels of sCD86, sCD95 and sCD95L were analyzed by solid phase sandwich enzyme-linked immunoabsorbent assays. Our results first showed that the pre-transplantation serum levels of sCD86 in the AR group were significantly higher than in the NAR group (1007±82U/mL vs. 739±46U/mL, p=0.006), and in the post-transplantation period these levels decreased sharply. Second, the levels of sCD95L and sCD95 in the pre-transplantation period did not point to statistically significant differences between the AR and NAR groups. Considering primary liver disease, the pre-transplantation levels of sCD86 and sCD95L in the VP group were significantly higher than those of the VN group (VP, 977±69U/mL vs. VN, 722±51U/mL, p<0.002, and VP, 482±78pg/mL vs. VN, 221±31pg/mL, p=0.002, respectively). Multivariate analysis revealed that only the pre-transplantation levels of sCD86 were independently associated with the development of episodes of acute rejection (p=0.005, OR=2.1, IC 95%=1.27-3.47). In conclusion, the present work shows that primary liver disease could influence the pre-transplantation levels of sCD86 and sCD95L. High pre-transplantation serum levels of sCD86 could favor the development of episodes of acute rejection.