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We aimed to evaluate whether CMV<\/jats:styled-content> serostatus may differ in patients with early MS<\/jats:styled-content> as compared with patients with non\u2010early MS<\/jats:styled-content>, analyzing the putative association of this virus with MS<\/jats:styled-content> clinical course and humoral immune responses against other herpesviruses.<\/jats:p><\/jats:sec>Methods<\/jats:title>Multicentric analysis was undertaken of 310 patients with MS<\/jats:styled-content> (early MS<\/jats:styled-content>, disease duration \u22645\u00a0years, n<\/jats:italic>\u00a0=\u00a0127) and controls (n<\/jats:italic>\u00a0=\u00a0155), evaluating specific humoral responses to CMV<\/jats:styled-content>, Epstein\u2013Barr virus and human herpesvirus\u20106, as well as T\u2010cell and natural killer (NK<\/jats:styled-content>)\u2010cell immunophenotypes.<\/jats:p><\/jats:sec>Results<\/jats:title>Cytomegalovirus seroprevalence in early MS<\/jats:styled-content> was lower than in non\u2010early MS<\/jats:styled-content> or controls (P<\/jats:italic>\u00a0<\u00a00.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01\u20131.08, P<\/jats:italic>\u00a0<\u00a00.05). CMV<\/jats:styled-content>+ patients with MS<\/jats:styled-content> displayed increased proportions of differentiated T\u2010cells (CD<\/jats:styled-content>27\u2212CD<\/jats:styled-content>28\u2212, CD<\/jats:styled-content>57+, LILRB<\/jats:styled-content>1+) and NKG<\/jats:styled-content>2C+ NK<\/jats:styled-content>\u2010cells, which were associated with a lower disability in early MS<\/jats:styled-content> (P<\/jats:italic>\u00a0<\u00a00.05). CMV<\/jats:styled-content>+ patients with early MS<\/jats:styled-content> had an age\u2010related decline in serum anti\u2010EBNA<\/jats:styled-content>\u20101 antibodies (P<\/jats:italic>\u00a0<\u00a00.01), but no CMV<\/jats:styled-content>\u2010related differences in anti\u2010human herpesvirus\u20106 humoral responses.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Low CMV<\/jats:styled-content> seroprevalence was observed in patients with early MS<\/jats:styled-content>. Modification of MS<\/jats:styled-content> risk attributed to CMV<\/jats:styled-content> might be related to the induction of differentiated T\u2010cell and NK<\/jats:styled-content>\u2010cell subsets and\/or modulation of Epstein\u2013Barr virus\u2010specific immune responses at early stages of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.13622","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T14:54:45Z","timestamp":1520866485000},"page":"925-933","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Low cytomegalovirus seroprevalence in early multiple sclerosis: a case for the \u2018hygiene hypothesis\u2019?"],"prefix":"10.1111","volume":"25","author":[{"given":"E.","family":"Alari\u2010Pahissa","sequence":"first","affiliation":[{"name":"Neurology Department Hospital del Mar Medical Research Institute (IMIM) Barcelona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Neurology Department Universitat Aut\u00f2noma de Barcelona Hospital del Mar Medical Research Institute (IMIM) Barcelona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Zabalza","sequence":"additional","affiliation":[{"name":"Neurology Department Hospital del Mar Medical Research Institute (IMIM) Barcelona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Alvarez\u2010Lafuente","sequence":"additional","affiliation":[{"name":"Neurology Service Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico de San Carlos Madrid"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Munteis","sequence":"additional","affiliation":[{"name":"Neurology Department Hospital del Mar Medical Research Institute (IMIM) Barcelona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Vera","sequence":"additional","affiliation":[{"name":"Neurology Department Hospital del Mar Medical Research Institute (IMIM) Barcelona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Arroyo","sequence":"additional","affiliation":[{"name":"Neurology Service Hospital Universitario Quir\u00f3nsaluld Madrid"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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