Correlation of Killer Immunoglobulin like Receptor Genes with the Rate of Cytomegalovirus Infection in Renal Transplantation Cases

Abstract

Aim: Immune mechanisms of Cytomegalovirus (CMV) infection suggest a possible relationship between CMV with development of acute graft rejection. Current immune suppression impairs antiviral specific T-cell immunity in solid organ transplantation. Inhibitory/ activating NK receptor bindings activated by self HLA antigens confront allogeneic cells that lack a ligand for specific receptor. KIR ligand incompatibility caused due to presence/absence of KIR receptor in recipient and corresponding HLA ligand by the allograft which is recognized by KIR, may have potential impact on chance of CMV infection and graft survival in renal transplantation recipient. We hypothesized that predominance of activating KIR genes may downplay the rate of CMV infection among kidney transplant recipients. Methods: We have evaluated matches/mismatches between KIR genes and known HLA ligands among CMV disease (n=27) and primary CMV infected (n=259) conditions among North Indian renal transplant cases. Sequence specific primed polymerase chain reaction method was used for KIR genotyping. Results: Survival analysis revealed increased CMV risk for individuals carrying inhibitory KIR genes 2DL1 (OR=3.45, p-value=0.013) and 3DL1(OR=3.23, p-value=0.032), while protective association was revealed for activating KIR2DS1 (OR=0.32, p-value=0.005). Compatible KIR2DL2-HLA-C1 combination showed protective association (OR=0.23, p=0.031) with its ligand HLA-Bw4. KIR-HLA ligand match-mismatch also revealed protective association (OR=0.95, p-value=0.014) in the absence of KIR3DS1-HLA-Bw4 combination. Conclusion: Graft outcome after renal transplantation revealed prolonged survival in the presence of certain KIR/HLA class I ligand combinations among CMV diseased and primary CMV infected cases.