Killer Immunoglobulin-like Receptor (KIR) and HLA Genotypes Affect the Outcome of Allogeneic Kidney Transplantation

BACKGROUND: Recipient NK cells may detect the lack of recipient's (i.e., self) HLA antigens on donor renal tissue by means of their killer cell immunoglobulin-like receptors (KIRs). KIR genes are differently distributed in individuals, possibly contributing to differences in response to allogeneic graft. METHODOLOGY/PRINCIPAL FINDINGS: We compared frequencies of 10 KIR genes by PCR-SSP in 93 kidney graft recipients rejecting allogeneic renal transplants with those in 190 recipients accepting grafts and 690 healthy control individuals. HLA matching results were drawn from medical records. We observed associations of both a full-length KIR2DS4 gene and its variant with 22-bp deletion with kidney graft rejection. This effect was modulated by the HLA-B,-DR matching, particularly in recipients who did not have glomerulonephritis but had both forms of KIR2DS4 gene. In contrast, in recipients with glomerulonephritis, HLA compatibility seemed to be much less important for graft rejection than the presence of KIR2DS4 gene. Simultaneous presence of both KIR2DS4 variants strongly increased the probability of rejection. Interestingly, KIR2DS5 seemed to protect the graft in the presence of KIR2DS4fl but in the absence of KIR2DS4del. CONCLUSIONS/SIGNIFICANCE: Our results suggest a protective role of KIR2DS5 in graft rejection and an association of KIR2DS4 with kidney rejection, particularly in recipients with glomerulonephritis.