Danilo Di Bona1, Valeria Scafidi2, Antonella Plaia3, Claudia Colomba4, Domenico Nuzzo2, Cecilia Occhino5, Antonino Tuttolomondo6, Giovanni Giammanco4, Simona De Grazia4, Giuseppe Montalto6, Giovanni Duro2, Marco Cippitelli7, Calogero Caruso1. 1. Unità Operativa di Medicina Trasfusionale, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" Palermo Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo. 2. Istituto di Biomedicina ed Immunologia Molecolare, Consiglio Nazionale delle Ricerche. 3. Dipartimento di Scienze Matematiche Statistiche e Aziendali, Università di Palermo. 4. Dipartimento di Scienze per la Promozione della Salute e Materno Infantile "G. D'Alessandro", Università di Palermo. 5. Unità Operativa di Malattie Infettive, Ospedali Riuniti Villa Sofia-Cervello. 6. Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo. 7. Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
Abstract
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 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. 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.
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 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. 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.