Killer cell immunoglobulin‐like receptor polymorphisms in HLA‐identical kidney transplant recipients: lack of 2DL2 and 2DS2 may be associated with poor graft function

Abstract

Killer cell immunoglobulin-like receptors (KIR) on natural killer cells mediate killing by recognizing class I presentation of peptides by infected or oncogenic cells. KIR differences in stem cell transplants have been implicated in increased graft vs host disease. Human leukocyte antigen (HLA)-matched-related kidney recipients have the best graft survival as compared to one haplotype-matched recipients. These HLA-identical transplant pairs may be ideal for studying minor HLA antigens and KIR polymorphic differences and their relation to graft function. We have studied KIR polymorphism in recipients and donor pairs of HLA-matched sibling kidney transplants to demonstrate differences in genotype as related to long-term graft function and/or chronic rejection. We employed a KIR genotyping kit (Dynal, Brown Deer, WI), that uses sequence-specific priming by PCR to identify 19 alleles for genotypes in 12 donor/recipient (D/R) pairs at least 1 year posttransplant. There were two pairs that had different alleles in the recipient that were not found in the donor. One pair had different alleles found in the donor that were not present in the recipient. Two pairs had difference in alleles in both the donor and recipient. Seven of the 12 pairs had the same KIR genotype. Eight of the 12 pairs (both donor and recipient) exhibited a haplotype with 2DL2+ and 2DS2+. Four of the 12 exhibited a haplotype 2DL2- and 2DS2-. Three out of four of these recipients had increased creatinine levels and at least one graded rejection episode. One of these three has lost their graft. In conclusion, the genotyping of HLA-matched sibling kidney transplant D/R pairs demonstrates that there may be an association of higher risk for poor graft function when both genotypes lack 2DL2 and 2DS2.