title: Expansion of the NKG2C+ natural killer-cell subset is associated with high-risk carotid atherosclerotic plaques in seropositive patients for human cytomegalovirus.
abstract: OBJECTIVE
  Human cytomegalovirus (HCMV), a pathogen involved in the development and progression of atherosclerosis, promotes in some individuals a marked reconfiguration of the natural killer (NK)-cell compartment whose hallmark is a persistent expansion of a peripheral blood NK-cell subset expressing the CD94/NKG2C NK receptor. We aimed to evaluate whether the HCMV-associated NK-cell compartment reconfiguration is related to carotid atherosclerotic plaque (CAP) instability.
  
  
  RESULTS
  NK receptor expression (ie, LILRB1, NKG2A, NKG2C, and killer immunoglobulin-like receptors [KIR]) by peripheral NK and T cells was evaluated in 40 patients with HCMV+ with CAP, including nonatherosclerotic strokes (n=15) and healthy subjects (n=11) as controls. High-risk CAP (n=16), defined as carotid stenosis >50% with ipsilateral neurological symptomatology in the previous 180 days, compared with non-high-risk CAP had higher %NKG2C+ NK cells (29.5 ± 22.4% versus 16.3 ± 13.2%; P=0.026; odds ratio, 1.053; 95% confidence interval, 1.002-1.106; P=0.042), with a corresponding reduction in the NKG2A+ NK subset (31.7 ± 17.8% versus 41.8 ± 15.8%; P=0.072). The proportions of NKG2C+ NK cells in high-risk CAP were inversely correlated with the CD4+/CD8+ ratio (R(Spearman)=-0.629; P=0.009) and directly with high-sensitivity C-reactive protein levels (R(Pearson) = 0.591; P=0.012), consistent with higher subclinical systemic inflammation. The intraplaque inflammatory infiltrate, evaluated in 27 CAP obtained after endarterectomy, showed a higher presence of subintimal CD3+ lymphocytes in those patients with HCMV-induced changes in the peripheral NK- and T-cell compartments.
  
  
  CONCLUSIONS
  The expansion of NKG2C+ NK cells in patients with CAP seems to be associated with an increased risk of plaque destabilization in some patients with chronic HCMV infection.
authors: From the Neurology Service (J.E.M.-R., R.R., E.C., A.O., J.R.) and Immunology Unit (A.M., M.L.-B.), Hospital del Mar Medical Research Institute (IMIM), Universitat Pompeu Fabra, Barcelona, Spain; and Department of Pathology (J.M.-C., T.B., F.A.) and Vascular Surgery Department (L.R.), Hospital del Mar, Universidad Autónoma de Barcelona, Barcelona, Spain.
authors: Jose Enrique
authors: JE
authors: Martínez-Rodríguez
authors: Jessica
authors: J
authors: Munné-Collado
authors: Raquel
authors: R
authors: Rasal
authors: Elisa
authors: E
authors: Cuadrado
authors: Luis
authors: L
authors: Roig
authors: Angel
authors: A
authors: Ois
authors: Aura
authors: A
authors: Muntasell
authors: Teresa
authors: T
authors: Baro
authors: Francesc
authors: F
authors: Alameda
authors: Jaume
authors: J
authors: Roquer
authors: Miguel
authors: M
authors: López-Botet
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D019002:CD56 Antigen / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000453:epidemiology* / Q000276:immunology*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D012307:Risk Factors; D016036:Seroepidemiologic Studies
chemical_list: D000914:Antibodies, Viral; D019002:CD56 Antigen; C527059:KLRC2 protein, human; C522918:NCAM1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C
keywords: NKG2C receptor; carotid artery diseases; cytomegalovirus; killer cells, natural