HLA and Killer Cell Immunoglobulin-like Receptors Influence the Natural Course of CMV Infection
HLA and Killer Cell Immunoglobulin-like Receptors Influence the Natural Course of CMV Infection
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DOI：
10.1093/infdis/jiu226
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发表时间：
2014-10-01
影响因子：
6.4
通讯作者：
Caruso, Calogero
中科院分区：
文献类型：
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作者：
Di Bona, Danilo;Scafidi, Valeria;Caruso, Calogero
背景自然杀伤（NK）细胞通过其表面受体（包括活化性和抑制性杀伤免疫球蛋白样受体（KIR））和人白细胞抗原（HLA）I类分子的相互作用提供对巨细胞病毒（CMV）感染的主要防御。本研究评估了KIR和HLA库是否可能影响免疫活性宿主原发性CMV感染后发生有症状或无症状疾病的风险。对60例免疫功能正常的原发性CMV感染患者进行KIR及其HLA配体基因分型，沿着60例既往无症状感染者作为对照。在有症状的患者中，纯合子A单倍型（只有KIR 2DS 4作为激活KIR）的频率高于对照组（分别为30%和12%;比值比[OR] = 3.24; P = 0.01）。Logistic回归分析显示，发生症状性疾病的风险与纯合A单倍型和HLABw 4（T）等位基因相关。结合两个独立变量，我们发现60例有症状患者中有37例（62%）具有纯合A单倍型或HLABw 4（T）等位基因，而60例对照中只有18例（30%）具有高度显著的OR（OR = 3.75，P < .0005）。携带纯合A单倍型或HLABw 4（T）等位基因的免疫活性受试者在原发性CMV感染后发生症状性疾病的风险更高。
Background. Natural killer (NK) cells provide a major defense against cytomegalovirus (CMV) infection through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulinlike receptors (KIRs), and human leukocyte antigens (HLA) class I molecules. This study assessed whether the KIR and HLA repertoire may influence the risk of developing symptomatic or asymptomatic disease after primary CMV infection in the immunocompetent host.Methods. Sixty immunocompetent patients with primary symptomatic CMV infection were genotyped for KIR and 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 symptomatic patients than controls (30% vs 12%, respectively; odds ratio [OR] = 3.24; P = .01). By logistic regression, the risk of developing symptomatic disease was associated with the homozygous A haplotype and the HLABw4(T) 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 HLABw4(T) allele with a highly significant OR (OR = 3.75, P < .0005).Conclusions. Immunocompetent subjects carrying the homozygous A haplotype or the HLABw4(T) allele are at higher risk of developing symptomatic disease after primary CMV infection.