HLA and killer cell immunoglobulin-like receptors influence the natural course of CMV infection

Background. Natural killer (NK) cells provide a major defense against cytomegalovirus (CMV) infectionthrough the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulinlikereceptors (KIRs), and human leukocyte antigens (HLA) class I molecules. This study assessed whether theKIR and HLA repertoire may influence the risk of developing symptomatic or asymptomatic disease after primaryCMV infection in the immunocompetent host.Methods. Sixty immunocompetent patients with primary symptomatic CMV infection were genotyped for KIRand their HLA ligands, along with 60 subjects with a previous asymptomatic infection as controls.Results. The frequency of the homozygous A haplotype (only KIR2DS4 as activating KIR) was higher in symptomaticpatients than controls (30% vs 12%, respectively; odds ratio [OR] = 3.24; P = .01). By logistic regression, therisk of developing symptomatic disease was associated with the homozygous A haplotype and the HLABw4T allele.Combining the 2 independent variables, we found that 37 out of 60 (62%) symptomatic patients but only 18 out of 60(30%) of controls possessed the homozygous A haplotype or the HLABw4T allele with a highly significant OR(OR = 3.75, P < .0005).Conclusions. Immunocompetent subjects carrying the homozygous A haplotype or the HLABw4T allele are athigher risk of developing symptomatic disease after primary CMV infection.