title: Adaptive natural killer cell response to cytomegalovirus and disability progression in multiple sclerosis.
abstract: 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.
  
  
  
  The purpose of this study was to evaluate whether the HCMV-driven NKG2C+ NK-cell expansion is related to the MS clinical course.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Neurology Department, Hospital del Mar Medical Research Institute, Spain JMartinezR@hospitaldelmar.cat.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Martínez-Rodríguez
authors.affiliation: Multiple Sclerosis Unit, University Hospital de Bellvitge, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cobo-Calvo
authors.affiliation: Immunology Department, Hospital Universitario Ramón y Cajal, Spain.
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Villar
authors.affiliation: Neurology Department, Hospital del Mar Medical Research Institute, Spain.
authors.forename: Elvira
authors.initials: E
authors.lastname: Munteis
authors.affiliation: Neurology Service, Hospital Clinic and Institut d'Investigació August Pi I Sunyer, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Blanco
authors.affiliation: Neurology Department, Hospital del Mar Medical Research Institute, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Rasal
authors.affiliation: Immunology Unit, University Pompeu Fabra, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vera
authors.affiliation: Hospital del Mar Medical Research Institute, Spain.
authors.forename: Aura
authors.initials: A
authors.lastname: Muntasell
authors.affiliation: Neurology Service, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Alvarez-Lafuente
authors.affiliation: Neurology Service, Hospital Clinic and Institut d'Investigació August Pi I Sunyer, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Saiz
authors.affiliation: Neurology Department, Ramon y Cajal University Hospital, Spain.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Alvarez-Cermeño
authors.affiliation: Multiple Sclerosis Unit, University Hospital de Bellvitge, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Martínez-Yélamos
authors.affiliation: Neurology Department, Hospital del Mar Medical Research Institute, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Roquer
authors.affiliation: Immunology Unit, University Pompeu Fabra, Spain/ Hospital del Mar Medical Research Institute, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Botet
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C
keywords: Cytomegalovirus; NKG2C; disability progression; herpesvirus; multiple sclerosis; natural killer cells