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: 11.91). 03/2006; 59(3):499-503. DOI: 10.1002/ana.20820
Source: PubMed

ABSTRACT 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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    • "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.
    BMC Neurology 10/2014; 14(1):196. DOI:10.1186/s12883-014-0196-x · 2.49 Impact Factor
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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.
    Frontiers in Microbiology 06/2014; 5:308. DOI:10.3389/fmicb.2014.00308 · 3.94 Impact Factor
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    • "While the infection is usually benign, it can in some cases lead to acute infectious mononucleosis and can impair the immune system [11,12]. EBV is linked to several malignancies, including Burkett’s lymphoma, post-transplant lymph-proliferative disease, Hodgkin’s disease, and several autoimmune diseases [13–15]. EBV inhibits the ability of lymphocytes to respond properly to antigens such as mitogenic lectins, concanavalin A, phytohemagglutinin, and pokeweed mitogen, among others [16,17]. "
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    ABSTRACT: Background Many natural compounds were tested for the ability to suppress viral replication. The present manuscript details an analysis of high dose vitamin C therapy on patients with EBV infection. Material and Methods The data were obtained from the patient history database at the Riordan Clinic. Among people in our database who were treated with intravenous vitamin C (7.5 g to 50 g infusions) between 1997 and 2006, 178 patients showed elevated levels of EBV EA IgG (range 25 to 211 AU) and 40 showed elevated levels of EBV VCA IgM (range 25 to 140 AU). Most of these patients had a diagnosis of chronic fatigue syndrome, with the rest being diagnosed as having mononucleosis, fatigue, or EBV infection. Results Our data provide evidence that high dose intravenous vitamin C therapy has a positive effect on disease duration and reduction of viral antibody levels. Plasma levels of ascorbic acid and vitamin D were correlated with levels of antibodies to EBV. We found an inverse correlation between EBV VCA IgM and vitamin C in plasma in patients with mononucleosis and CFS meaning that patients with high levels of vitamin C tended to have lower levels of antigens in the acute state of disease. In addition, a relation was found between vitamin D levels and EBV EA IgG with lower levels of EBV early antigen IgG for higher levels of vitamin D. Conclusions The clinical study of ascorbic acid and EBV infection showed the reduction in EBV EA IgG and EBV VCA IgM antibody levels over time during IVC therapy that is consistent with observations from the literature that millimolar levels of ascorbate hinder viral infection and replication in vitro.
    Medical science monitor: international medical journal of experimental and clinical research 05/2014; 20:725-32. DOI:10.12659/MSM.890423 · 1.22 Impact Factor
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