EBV and CMV viral load was measured on a single occasion in each patient; each sample was tested in triplicate. in HLA-A*02?/B*07+/DRB1*15+ patients and lowest in HLA-A*A02+/B*07?/DRB1*15? individuals (p? ?0.0001). HLA-B*07 resulted the most associated allele to EBV VL after multiple regression analysis considering altogether the three alleles, (p?=?0.0001). No differences were observed in anti-EBV antibody titers in relationship with HLA distribution. Conclusions Host HLA-B*07 allele influence Ceramide EBV VL in MS. As HLA-class I molecules present antigens to T lymphocytes and initiate immune response against viruses, these results could support a role for EBV in MS. Electronic supplementary material Ceramide The online version of this article (10.1186/s12967-018-1450-6) contains supplementary material, which is available to authorized users. family, subfamily, genus . The computer virus is a worldwide pathogen and is persistently harbored by almost all adults regardless of health or geographic location. In western countries, with high standard of living, primary EBV contamination occurs commonly in adolescence, and might cause infectious mononucleosis (IM) in a minority of cases. EBV replicates in oropharyngeal epithelial cells during primary disease and subsequently establishes Ceramide a latent contamination in circulating B lymphocytes. IM and elevated titers of antibodies against EBV nuclear antigens (EBNA) have been associated to an increased risk to develop MS and, on the other hand, lack of EBV contamination correlates with a lower risk to develop the disease . Other epidemiologic results suggesting a role for EBV in the pathogenesis of MS include the observations that EBV-infected B cells and plasma cells accumulate in the brain of MS patients  and a strong EBV specific cell-mediated immune responses are seen in these patients [11, 12]. Moreover, evidences of EBV DNA or transcripts in brain or cerebrospinal fluid of MS individuals remains controversial , as reported by some papers [10, 14], but not confirmed by other authors [15C17]. Confliting results are reported on possible correlations between HLA alleles, EBV contamination, and MS [18, 19]. Thus, an conversation between HLA-class I alleles and reactivity to EBV-related epitopes was recently shown, suggesting that this mechanism through which HLA genes influence Ceramide the risk of developing MS may involve EBV-specific immune responses [18, 20]. Other data showed that HLA-B*7 allele is usually associated with increased EBV-specific Ab titers, higher disability scores, and a more compromised MRI pattern in MS patients . We verified Ceramide if correlations could be established between protective/risk HLA-class I alleles and EBV-specific parameters in MS; results suggest that this is indeed the case. Methods Study populace and specimens A total of 206 individuals were enrolled in the study: 117 Rabbit Polyclonal to EDNRA of them (mean age: 44.7??12.6?years) were patients with a diagnosis of MS according to revised McDonald criteria ; these patients are followed by the Multiple Sclerosis Unit of the Don C. Gnocchi Foundation, IRCCS S. Maria Nascente in Milan, Italy, and by the MS Centers of the PROGEMUS Consortium, coordinated at the University of Piemonte Orientale. The remaining 89 individuals (mean age: 44.8??10.8?years) were age- and sex-matched healthy controls (HC), who donate blood at the same institutions. HC and MS patients were selected in order to obtain comparable distribution of HLA-B*07, -A*02 and -DRB1*15 frequency. All individuals were EBV-seropositive. The study conformed to the ethical principles of the Declaration of Helsinki; all subjects gave informed and written consent according to a protocol approved by the local ethics committee of the centers. Whole blood and serum samples were collected from all the individuals enrolled in the study. Whole blood was utilized for DNA extraction, whereas serum samples, obtained by centrifugation for 10?min at 1800at room heat, were aliquoted into sterile cryovials and stored at ??20?C..