Adaptive natural killer cell response to cytomegalovirus and disability progression in multiple sclerosis. (May 2016)

• Record Type: Journal Article
• Authors: Martínez-Rodríguez, Jose E; Cobo-Calvo, Alvaro; Villar, Luisa M; Munteis, Elvira; Blanco, Yolanda; Rasal, Raquel; Vera, Andrea; Muntasell, Aura; Alvarez-Lafuente, Roberto; Saiz, Albert; Alvarez-Cermeño, Jose C; Martínez-Yélamos, Sergio; Roquer, Jaume; López-Botet, Miguel
• Is Part Of: Multiple sclerosis. Volume 22:Number 6(2016)
• Page Start: 741
• Page End: 752
• Publication Date: 2016-05
• Subjects: Cytomegalovirus -- disability progression -- herpesvirus -- multiple sclerosis -- natural killer cells -- NKG2C; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458515601215
• Languages: English
• ISSNs: 1352-4585

Abstract

Background: Human cytomegalovirus (HCMV) causes a highly prevalent infection which may have a multifaceted impact on chronic inflammatory disorders. However, its potential influence in multiple sclerosis (MS) remains controversial. The HCMV-host interaction may induce an adaptive reconfiguration of the natural killer (NK) cell compartment, whose hallmark is a persistent expansion of peripheral NKG2C+ NK-cells. Objective: The purpose of this study was to evaluate whether the HCMV-driven NKG2C+ NK-cell expansion is related to the MS clinical course. Methods: Multicentre analysis of NKG2C expression and genotype according to HCMV serostatus and time of assignment of irreversible disability scores in 246 MS patients prospectively followed up in our institutions. Results: NKG2C expression was unrelated to disease-modifying drugs, remained stable under steady-state conditions, and was higher in HCMV(+) NKG2C +/+ homozygous individuals. NKG2C+ NK-cell expansion in HCMV(+) patients, as compared to HCMV(+) or HCMV(–) patients with lower NKG2C+ NK-cells proportions, conferred a lower risk of progression in Cox regression analysis (Expanded Disability Status Scale (EDSS)>3.0, hazard ratio (HR)=0.33, 95% confidence interval (CI) 0.15–0.71, p =0.005; EDSS>5.5, HR=0.23, 95% CI 0.07-0.74, p =0.014). Neither HCMV serostatus nor NKG2C genotype appeared to be related to disability progression. Conclusions: HCMV may exert a beneficial influence on MS, decreasing the risk of disability progression in those patients displaying a virus-driven NKG2C+ NK-cell expansion.