Infectious mononucleosis and risk for multiple sclerosis: A meta-analysis

Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Annals of Neurology (Impact Factor: 9.98). 03/2006; 59(3):499-503. DOI: 10.1002/ana.20820
Source: PubMed


To characterize the association between infectious mononucleosis (IM), a frequent clinical manifestation of primary Epstein-Barr virus infection after childhood, and the risk for multiple sclerosis (MS).
We conducted a systematic review and meta-analysis of case-control and cohort studies of IM and MS.
The combined relative risk of MS after IM from 14 studies was 2.3 (95% confidence interval, 1.7-3.0; p < 10(-8)). Potential sources of heterogeneity (ie, study design, MS definition, and latitude) barely influenced our results.
We conclude that Epstein-Barr virus infection manifesting as IM in adolescents and young adults is a risk factor for MS.

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    • "In a meta-analysis including 18 articles, and totalizing 19,390 MS patients and controls,Handel et al.showed that the risk of developing MS after IM was 2.17 times higher than when one contracted EBV asymptomatically (P = 10 À54 !)[13]. The interval between IM and MS is comprised between five to 10 years[9,14,15]. Altogether, these data are consistent with the fact that adolescence is a critical period in terms of immunology related to MS (see also the discussion on vitamin D[VitD]). The risk of MS increases linearly with the increase of anti-Epstein-Barr nuclear antigen-1 (EBNA-1)-specific IgG[16]. "
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    ABSTRACT: Although multiple sclerosis (MS) is recognized as a disorder involving the immune system, the interplay of environmental factors and individual genetic susceptibility seems to influence MS onset and clinical expression, as well as therapeutic responsiveness. Multiple human epidemiological and animal model studies have evaluated the effect of different environmental factors, such as viral infections, vitamin intake, sun exposure, or still dietary and life habits on MS prevalence. Previous Epstein-Barr virus infection, especially if this infection occurs in late childhood, and lack of vitamin D (VitD) currently appear to be the most robust environmental factors for the risk of MS, at least from an epidemiological standpoint. Ultraviolet radiation (UVR) activates VitD production but there are also some elements supporting the fact that insufficient UVR exposure during childhood may represent a VitD-independent risk factor of MS development, as well as negative effect on the clinical and radiological course of MS. Recently, there has been a growing interest in the gut-brain axis, a bidirectional neuro-hormonal communication system between the intestinal microbiota and the central nervous system (CNS). Indeed, components of the intestinal microbiota may be pro-inflammatory, promote the migration of immune cells into the CNS, and thus be a key parameter for the development of autoimmune disorders such as MS. Interestingly most environmental factors seem to play a role during childhood. Thus, if childhood is the most fragile period to develop MS later in life, preventive measures should be applied early in life. For example, adopting a diet enriched in VitD, playing outdoor and avoiding passive smoking would be extremely simple measures of primary prevention for public health strategies. However, these hypotheses need to be confirmed by prospective evaluations, which are obviously difficult to conduct. In addition, it remains to be determined whether and how VitD supplementation in adult life would be useful in alleviating the course of MS, once this disease has already started. A better knowledge of the influence of various environmental stimuli on MS risk and course would certainly allow the development of add-on therapies or measures in parallel to the immunotherapies currently used in MS. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    Full-text · Article · Mar 2015 · La Presse Médicale
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    • "A history of infectious mononucleosis (IM), the clinical manifestation of infection with EBV, is reported to give two to threefold increased risk of MS [11] and EBV seronegative individuals have a very low risk of MS [2]. Since infection with EBV in childhood often is asymptomatic, an episode of IM has been suggested as an indicator of low exposures to infections early in life [11]. Further, an interaction between antibodies against EBV nuclear antigen 1 and HLA-DRB1*15:01 status has been suggested [12,13]. "
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    ABSTRACT: Background Several environmental exposures, including infection with Epstein-Barr virus, low levels of vitamin D and smoking are established risk factors for multiple sclerosis (MS). Also, high hygienic standard and infection with parasites have been proposed to influence MS risk. The aim of this study was to investigate the influence of various environmental exposures on MS risk in a Norwegian cohort, focusing on factors during childhood related to the hygiene hypothesis.MethodsA questionnaire concerning environmental exposures, lifestyle, demographics and comorbidity was administrated to 756 Norwegian MS patients and 1090 healthy controls. Logistic regression was used to calculate odds ratio (OR) with 95% confidence interval (CI) for the risk of MS associated with the variables infectious mononucleosis, severe infection during childhood, vaccination and animals in the household during childhood. Age, gender, HLA-DRB1*15:01, smoking and infectious mononucleosis were included as covariates. General environmental exposures, including tobacco use, were also evaluated.ResultsInfectious mononucleosis was confirmed to be significantly associated with increased MS risk, also after adjusting for the covariates (OR¿=¿1.79, 95% CI: 1.12-2.87, p¿=¿0.016). The controls more often reported growing up with a cat and/or a dog in the household, and this was significant for ownership of cat also after adjusting for the covariates (OR¿=¿0.56, 95% CI: 0.40-0.78, p¿=¿0.001). More patients than controls reported smoking and fewer patients reported snuff use.Conclusions In this Norwegian MS case¿control study of environmental exposures, we replicate that infectious mononucleosis and smoking are associated with increased MS risk. Our data also indicate a protective effect on MS of exposure to cats during childhood, in accordance with the hypothesis that risk of autoimmune diseases like MS may increase with high hygienic standard.
    Full-text · Article · Oct 2014 · BMC Neurology
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    • "Therefore, it should be feasible to define important DC populations that initiate EBV-specific immune control by for example antibody depletion (Meixlsperger et al., 2013), in order to then refine vaccination approaches that protect from EBV infection challenge. With such smart vaccine formulations that are directed against the most relevant DC populations EBV negative adolescents with a high risk to suffer symptomatic EBV infection could be vaccinated and their predisposition to develop Hodgkin’s lymphoma or multiple sclerosis attenuated (Hjalgrim et al., 2003; Thacker et al., 2006). "
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    ABSTRACT: Epstein Barr virus (EBV) causes persistent infection in more than 90% of the human adult population and is associated with 2% of all tumors in humans. This γ-herpes virus infects primarily human B and epithelial cells, but it has been reported to be sensed by dendritic cells (DCs) during primary infection. These activated DCs are thought to contribute to innate restriction of EBV infection and initiate EBV-specific adaptive immune responses via cross-priming. The respective evidence and their potential importance for EBV-specific vaccine development will be discussed in this review.
    Full-text · Article · Jun 2014 · Frontiers in Microbiology
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