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.

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 (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 HCMVinduced changes in the peripheral NK-and T-cell compartments. antibodies, which only partially reflect the complexity of the host-pathogen relationship. Conclusions-TheIn this context, herpesviruses may have a substantial effect in the progression of atherosclerosis and the cardiovascular risk.7 Among them, human cytomegalovirus (HCMV) is thought to be involved in the development of atherosclerosis based on clinico-epidemiological and experimental studies and has been proposed to contribute to the progression of the carotid plaque thickness 4 and the degree of stenosis. 8,9 In healthy individuals, HCMV remains latent, establishing a persistent infection and eventually undergoing subclinical reactivations. A remarkable fraction of the CD8+ T-cell compartment may be directed against HCMV, a phenomenon that has been associated with immunosenescence, leading in some aged healthy individuals to a reduction of the CD4+/CD8+ T-cell ratio. [10][11][12] In addition, HCMV has been shown to promote a persistent expansion of a peripheral blood NK-cell subset expressing high levels of the CD94/ NKG2C+ lectin-like receptor, 13 detectable to a variable degree in healthy subjects. 14 We hypothesize that the contribution of HCMV infection to atherosclerosis may depend on features of the host-pathogen relationship not reflected by the simple serological status. In the present study, the relationship of the HCMV-associated NK-cell compartment reconfig...

We have genotyped the 58 STRs (27 autosomal, 24 Y-STRs and 7 X-STRs) and 94 autosomal SNPs in Illumina ForenSeq™ Primer Mix A in 88 Spanish Roma (Gypsy) samples and 143 Catalans. Since this platform is based in massive parallel sequencing, we have used simple R scripts to uncover the sequence variation in the repeat region. Thus, we have found, across 58 STRs, 541 length-based alleles, which, after considering repeat-sequence variation, became 804 different alleles. All loci in both populations were in Hardy-Weinberg equilibrium. F between both populations was 0.0178 for autosomal SNPs, 0.0146 for autosomal STRs, 0.0101 for X-STRs and 0.1866 for Y-STRs. Combined a priori statistics showed quite large; for instance, pooling all the autosomal loci, the a priori probabilities of discriminating a suspect become 1-(2.3×10) and 1-(5.9×10), for Roma and Catalans respectively, and the chances of excluding a false father in a trio are 1-(2.6×10) and 1-(2.0×10).