Alari-Pahissa, ElisendaMoreira Villanueva, AntíaZabalza, AnaAlvarez-Lafuente, RobertoMunteis Olivas, ElviraVera, AndreaArroyo, RafaelÁlvarez Cermeño, Jose CarlosVillar, Luisa MariaLópez-Botet, M. (Miguel)Martínez-Rodriguez, José E.2018-11-072018Alari-Pahissa E, Moreira A, Zabalza A, Alvarez-Lafuente R, Munteis E, Vera A et al. Low cytomegalovirus seroprevalence in early multiple sclerosis: a case for the 'hygiene hypothesis'? Eur J Neurol. 2018 Jul;25(7):925-33. DOI: 10.1111/ene.136221351-5101http://hdl.handle.net/10230/35714BACKGROUND AND PURPOSE: Cytomegalovirus (CMV) infection has recently been associated with a lower multiple sclerosis (MS) susceptibility, although it remains controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early-life viral infections. We aimed to evaluate whether CMV serostatus may differ in patients with early MS as compared with patients with non-early MS, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses. METHODS: Multicentric analysis was undertaken of 310 patients with MS (early MS, disease duration ≤5 years, n = 127) and controls (n = 155), evaluating specific humoral responses to CMV, Epstein-Barr virus and human herpesvirus-6, as well as T-cell and natural killer (NK)-cell immunophenotypes. RESULTS: Cytomegalovirus seroprevalence in early MS was lower than in non-early MS or controls (P < 0.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01-1.08, P < 0.05). CMV+ patients with MS displayed increased proportions of differentiated T-cells (CD27-CD28-, CD57+, LILRB1+) and NKG2C+ NK-cells, which were associated with a lower disability in early MS (P < 0.05). CMV+ patients with early MS had an age-related decline in serum anti-EBNA-1 antibodies (P < 0.01), but no CMV-related differences in anti-human herpesvirus-6 humoral responses. CONCLUSIONS: Low CMV seroprevalence was observed in patients with early MS. Modification of MS risk attributed to CMV might be related to the induction of differentiated T-cell and NK-cell subsets and/or modulation of Epstein-Barr virus-specific immune responses at early stages of the disease.application/pdfengThis is the peer reviewed version of the following article: Alari-Pahissa E, Moreira A, Zabalza A, Alvarez-Lafuente R, Munteis E, Vera A. et al. Low cytomegalovirus seroprevalence in early multiple sclerosis: a case for the 'hygiene hypothesis'?. Eur J Neurol. 2018 Jul;25(7):925-933, which has been published in final form at http://dx.doi.org/10.1111/ene.13622. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.CitomegalovirusEsclerosi múltipleinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1111/ene.13622Epstein-Barr virusCytomegalovirusHerpesvirusHygiene hypothesisImmunosenescenceMultiple sclerosisNatural killer cellsinfo:eu-repo/semantics/openAccess