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

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• dc.contributor.author Alari-Pahissa, Elisenda
• dc.contributor.author Moreira Villanueva, Antía
• dc.contributor.author Zabalza, Ana
• dc.contributor.author Alvarez-Lafuente, Roberto
• dc.contributor.author Munteis Olivas, Elvira
• dc.contributor.author Vera, Andrea
• dc.contributor.author Arroyo, Rafael
• dc.contributor.author Álvarez Cermeño, Jose Carlos
• dc.contributor.author Villar, Luisa Maria
• dc.contributor.author López-Botet, M. (Miguel)
• dc.contributor.author Martínez-Rodriguez, José E.
• dc.date.accessioned 2018-11-07T08:37:17Z
• dc.date.issued 2018
• dc.description.abstract 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.
• dc.description.sponsorship This work was supported by grants FIS/PI14/00177,FIS/PI17/00254 and SAF 2013-49063-C2-1-R (SpanishMinistry of Economy and Competitiveness and FEDER), the EU FP7-MINECO Infect-ERA Pro-gram (PCIN-2015-191-C02-01) and Red Española de Esclerosis Múltiple from the Instituto de Salud CarlosIII, European Regional Development Fund (grant RD16/0015/0011) and Spanish Ministry of Economyand Competitiveness.
• dc.format.mimetype application/pdf
• dc.identifier.citation 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):925-33. DOI: 10.1111/ene.13622
• dc.identifier.doi http://dx.doi.org/10.1111/ene.13622
• dc.identifier.issn 1351-5101
• dc.identifier.uri http://hdl.handle.net/10230/35714
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof European Journal of Neurology. 2018 Jul;25(7):925-33
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-49063-C2-1-R
• dc.rights This 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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Epstein-Barr virus
• dc.subject.keyword Cytomegalovirus
• dc.subject.keyword Herpesvirus
• dc.subject.keyword Hygiene hypothesis
• dc.subject.keyword Immunosenescence
• dc.subject.keyword Multiple sclerosis
• dc.subject.keyword Natural killer cells
• dc.subject.other Citomegalovirus
• dc.subject.other Esclerosi múltiple
• dc.title Low cytomegalovirus seroprevalence in early multiple sclerosis: a case for the 'hygiene hypothesis'?
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion