Expansion of the NKG2C+ natural killer-cell subset is associated with high-risk carotid atherosclerotic plaques in seropositive patients for human cytomegalovirus

Jose Enrique Martínez-Rodríguez, Jessica Munné-Collado, Raquel Rasal, Elisa Cuadrado, Luis Roig, Angel Ois, Aura Muntasell, Teresa Baro, Francesc Alameda, Jaume Roquer, Miguel López-Botet

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23 Citations (Scopus)

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. APPROACH AND 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 (RSpearman=-0.629; P=0.009) and directly with high-sensitivity C-reactive protein levels (RPearson=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. © 2013 American Heart Association, Inc.
Original languageEnglish
Pages (from-to)2653-2659
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume33
Issue number11
DOIs
Publication statusPublished - 1 Nov 2013

Keywords

  • carotid artery diseases
  • cytomegalovirus
  • killer cells, natural
  • NKG2C receptor

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    Martínez-Rodríguez, J. E., Munné-Collado, J., Rasal, R., Cuadrado, E., Roig, L., Ois, A., Muntasell, A., Baro, T., Alameda, F., Roquer, J., & López-Botet, M. (2013). Expansion of the NKG2C+ natural killer-cell subset is associated with high-risk carotid atherosclerotic plaques in seropositive patients for human cytomegalovirus. Arteriosclerosis, Thrombosis, and Vascular Biology, 33(11), 2653-2659. https://doi.org/10.1161/ATVBAHA.113.302163