Donor and recipient HLA/KIR genotypes do not predict liver transplantation outcome

Abstract

Whether or not Natural Killer (NK) cells affect the immune response to solid organ allografts is still controversial. Main determinants of NK-cell activation are specific HLA/killer-cell immunoglobulin-like receptors (KIR) interactions that, in transplantation, may induce NK-cell alloreactivity. So far, in liver transplantation (LTX) donor-versus-recipient alloreactivity has not been investigated; in addition, studies of predicted recipient-versus-donor NK-cell alloreactivity have led to contradicting results. We typed a cohort of LTX donors and recipients for HLA-C/Bw4 and KIRs. We estimated the effect of NK-cell alloreactivity, as predicted by classically used models, in the donor-versus-recipient direction. The results indicate that HLA/KIR mismatches in the donor-versus-recipient direction do not predict graft rejection nor graft or patient survival, suggesting that donor-derived NK cells do not play a major role in LTX outcome. In addition, when considering predicted NK-cell alloreactivity in the reverse direction (recipient-versus-donor), we first confirmed that donor HLA-C genotype was not associated with acute rejection, graft or patient survival and secondly we found that none of the models describing NK-cell alloreactivity could predict LTX outcome. Overall our observations suggest that, in contrast to what is shown in haematopoietic stem cell transplantation, donor-derived NK cells may not contribute in preventing liver graft rejection, and that recipient-versus-donor NK-cell alloreactivity does not predict LTX outcome.