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.

9 Reads
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    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 · 2.04 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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 · 3.99 Impact Factor
  • Source
    • "While EBV establishes persistent infection usually without symptoms in small children, adolescents suffer frequently from infectious mononucleosis (IM) after primary EBV infection (Luzuriaga and Sullivan, 2010). IM confers increased risks for developing EBV associated Hodgkin's lymphoma and multiple sclerosis (Hjalgrim et al., 2003; Thacker et al., 2006; Nielsen et al., 2009). Thus, it is important to understand why EBV causes IM when primary infection is delayed. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epstein Barr virus (EBV) was the first human tumor virus to be identified. Despite 50years of research on this oncogenic virus, no therapeutic or prophylactic vaccine is available against this pathogen. In part, the development of such a vaccine is hampered by the lack of in vivo models for EBV infection and immune control. However, with the advent of mice with reconstituted human immune system components (HIS mice), certain aspects of EBV associated diseases and immune responses can be modeled in vivo. In this review, we will discuss the insights that can be gained from these experiments, and how immune system components can be manipulated to interrogate their function during EBV infection. Finally, we will compare EBV immunobiology in HIS mice to infection by EBV-related viruses in monkeys, and we will outline the strengths and weaknesses of these two in vivo models of EBV infection. Both of these models show great promise as a platform for preclinical EBV vaccine testing.
    Journal of immunological methods 05/2014; 410. DOI:10.1016/j.jim.2014.04.009 · 1.82 Impact Factor
Show more

Similar Publications

Preview (2 Sources)

9 Reads
Available from