HLA and KIR Interaction in Patients with Ischemic Stroke

Background: T-cells expressing the KIR2DS2 activating receptor were found to be prevalent in the coronary culprit atherosclerotic plaque in patients with acute coronary syndromes (ACS), suggesting a possible cytolytic activity against the endothelium of the plaque, leading to plaque rupture and in turn to superimposed thrombosis and sudden occlusion of the artery. To explore if a similar pathogenetic mechanism occurs in acute ischemic stroke, we analyzed the possible association between the genetic KIR and HLA repertoire and the susceptibility to ischemic stroke. Methods: Fourteen patients with ischemic stroke and ten controls with atherosclerotic disease without ischemic stroke matched for sex and age were genotyped for KIR and their HLA ligands, using PCR-SSP. Results: The frequency of the homozygous A haplotype (only KIR2DS4 as activating KIR) was 57% in patients and 80% controls (OR=0.33). The total number of activating and inhibitory KIR was not significantly different between cases and controls. The HLA-A was present in four cases and one control. The HLABw4T and HLABw4I alleles, as well as either the homozygous or the heterozygous form, were present in 12 cases and 6 controls, respectively. The putative interaction between HLABw4T/I allele and the KIR3DL1 inhibitory receptor was reported in 12 cases and 6 controls (OR=4). Conclusions: This descriptive preliminary analysis shows that subjects with ischemic stroke have a lower frequency of the A-haplotype, a higher frequency the HLABw4T or HLABw4I allele and a higher frequency of the HLABw4T/I-KIR3DL1 inhibitory interaction compared to controls, suggesting a stronger potential inhibition on NK activation.