Di Bona Danilo, Scafidi Valeria, Plaia Antonella, Colomba Claudia, Nuzzo Domenico, Occhino Cecilia, Tuttolomondo Antonino, Giammanco Giovanni, De Grazia Simona, Montalto Giuseppe, Duro Giovanni, Cippitelli Marco, Caruso Calogero
Unità Operativa di Medicina Trasfusionale, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" Palermo Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo.
Istituto di Biomedicina ed Immunologia Molecolare, Consiglio Nazionale delle Ricerche.
J Infect Dis. 2014 Oct 1;210(7):1083-9. doi: 10.1093/infdis/jiu226. Epub 2014 Apr 15.
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 immunoglobulin-like 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.
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.
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).
Immunocompetent subjects carrying the homozygous A haplotype or the HLABw4(T) allele are at higher risk of developing symptomatic disease after primary CMV infection.
自然杀伤(NK)细胞通过其表面受体(包括激活型和抑制型杀伤细胞免疫球蛋白样受体(KIR))与人类白细胞抗原(HLA)I类分子的相互作用,为抵抗巨细胞病毒(CMV)感染提供主要防御。本研究评估了KIR和HLA库是否会影响免疫功能正常宿主原发性CMV感染后出现有症状或无症状疾病的风险。
对60例原发性有症状CMV感染的免疫功能正常患者进行KIR及其HLA配体基因分型,同时选取60例既往无症状感染的受试者作为对照。
有症状患者中纯合A单倍型(仅KIR2DS4作为激活型KIR)的频率高于对照组(分别为30%和12%;优势比[OR]=3.24;P = 0.01)。通过逻辑回归分析,出现有症状疾病的风险与纯合A单倍型和HLA - Bw4(T)等位基因相关。综合这两个独立变量,我们发现60例有症状患者中有37例(62%)但对照组60例中只有18例(30%)具有纯合A单倍型或HLA - Bw4(T)等位基因,优势比非常显著(OR = 3.75,P < 0.0005)。
携带纯合A单倍型或HLA - Bw4(T)等位基因的免疫功能正常受试者在原发性CMV感染后出现有症状疾病的风险更高。