Low cytomegalovirus seroprevalence in early multiple sclerosis: a case for the ‘hygiene hypothesis’?

E. Alari-Pahissa, A. Moreira, A. Zabalza, R. Alvarez-Lafuente, E. Munteis, A. Vera, R. Arroyo, J. C. Alvarez-Cermeño, L. M. Villar, M. López-Botet, J. E. Martínez-Rodríguez

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    14 Citations (Scopus)


    © 2018 EAN Background 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.
    Original languageEnglish
    Pages (from-to)925-933
    JournalEuropean Journal of Neurology
    Issue number7
    Publication statusPublished - 1 Jul 2018


    • Epstein–Barr virus
    • cytomegalovirus
    • herpesvirus
    • hygiene hypothesis
    • immunosenescence
    • multiple sclerosis
    • natural killer cells


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