PHERV-W ENV and syncytin-1, the envelope proteins of the human endogenous retrovirus W family (HERV-W), have been proposed as etiological factors for MS development. In addition, herpesviruses, such as the Epstein-Barr virus (EBV) and the human herpesvirus 6A/B (HHV-6A/B), have been also strongly associated with the disease. This work aims to study the possible link between viral loads and antibody titers against EBV and HHV-6A/B and the pHERV-W ENV/syncytin-1 protein/gene expression. For this purpose, we conducted a 12-month longitudinal study involving 98 RRMS patients. Peripheral blood samples were obtained from each patient. Serum antibody titers against EBV and HHV-6A/B were determined by ELISA, while viral loads were analyzed using qPCR. HLA MS-related alleles were also genotyped. pHERV-W ENV/syncytin-1 protein and gene expression levels in immune cells were assessed by flow cytometry and qPCR, respectively. We found that the 12-month variation of the pHERV-W ENV gene expression levels positively correlated with the variation of the EBV viral load, especially in those patients with high baseline EBV loads. Therefore, these results could support previous studies pointing to the transactivation of pHERV-W ENV by EBV. However, further studies are needed to better understand this possible relationship.
Although the etiology of multiple sclerosis (MS) is still unknown, it is commonly accepted that environmental factors could contribute to the disease. The objective of this study was to analyze the humoral response to Epstein-Barr virus, human herpesvirus 6A/B and cytomegalovirus, and the levels of 25-hydroxyvitamin D (25(OH)D) and the three main short-chain fatty acids (SCFA), propionate (PA), butyrate (BA) and acetate (AA), in MS patients and healthy controls (HC) to understand how they could contribute to the pathogenesis of the disease. With this purpose, we analyzed the correlations among them and with different clinical variables and a wide panel of cell subsets. We found statistically significant differences for most of the environmental factors analyzed when we compared MS patients and HC, supporting their possible involvement in the disease. The strongest correlations with the clinical variables and the cell subsets analyzed were found for 25(OH)D and SCFAs levels. A correlation was also found between 25(OH)D and PA/AA ratio, and the interaction between these factors negatively correlated with interleukin 17 (IL-17)-producing CD4+ and CD8+ T cells in untreated MS patients. Therapies that simultaneously increase vitamin D levels and modify the proportion of SCFA could be evaluated in the future.
Background: Low levels of 25-hydroxyvitamin D (25(OH)D) have been described as one of the possible environmental factors involved in multiple sclerosis (MS) etiopathogenesis. Objectives: To study epidemiology of MS and 25(OH)D serum levels of patients in Lanzarote (29°02′06″N), a region with high ultraviolet radiation values during the whole year which is located far apart from Iberian Peninsula (36°–43°N), but without genetic/ethnic differences with it. Methods: Incidence in Lanzarote was assessed according to McDonald 2005 criteria between January 2008 and December 2015 and prevalence date was 12/31/15. For 25(OH)D serum levels analyses, samples from 60 MS patients and 60 healthy donors (HD) were collected monthly in a one-year prospective study. Results: The prevalence of MS in Lanzarote was 50.0/100,000 and the incidence per year was 2.5/100,000. Median 25(OH)D levels values were 29.1 ng/ml for MS patients (maximum = 36.1 ng/ml, minimum = 22.5 ng/ml) and 27.1 ng/ml for HD (maximum = 34.8 ng/ml, minimum = 22.8 ng/ml). There were no significant differences between 25(OH)D serum levels between MS patients and HD. Conclusions: Lanzarote possesses lower prevalence and incidence values than peninsular Spain. Moreover, 25(OH)D serum levels do not differ between MS patients and HD.