Multiple Sclerosis After Infectious Mononucleosis

Nielsen, Trine Rasmussen; Rostgaard, Klaus; Nielsen, Nete Munk; Koch‐Henriksen, Nils; Haahr, S; Sørensen, Per Soelberg; Hjalgrim, Henrik

doi:10.1001/archneur.64.1.72

Cited by 184 publications

(156 citation statements)

References 21 publications

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“…Furthermore, the genes encoding CYP27B1 and CYP24A1 could be epigenetically regulated [Kim et al 2009;Novakovic et al 2009], which may influence the vitamin D serum level and MS risk [Burrell et al 2011]. Moreover, interactions between CYP27B1 and HLA-DRB1*15 may exist and influence the MS risk [Simon et al 2011 [Thacker et al 2006;Nielsen et al 2007b;Ramagopalan et al 2009c;Handel et al 2010b]. Furthermore, plasma antibody titres against the EBV nuclear antigen 1 (EBNA1) increase several years before the clinical onset of MS [Sundström et al 2004;Levin et al 2005;Lünemann et al 2010;Sundqvist et al 2012a], EBNA1 levels are correlated with MS risk [Lucas et al 2011a;Munger et al 2011b;Simon et al 2012b] and antibody response to EBV antigens is generally higher in MS [Lindsey et al 2012].…”

Section: Genetic Risk Factors For Multiple Sclerosis Possibly Involvimentioning

confidence: 99%

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Pierrot‐Deseilligny

Souberbielle

2013

Ther Adv Neurol Disord

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Abstract:The contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis (MS) is reviewed. Among the multiple recently discovered actions of vitamin D, an immunomodulatory role has been documented in experimental autoimmune encephalomyelitis and in humans. This action in the peripheral immune system is currently the main known mechanism through which vitamin D might influence MS, but other types of actions could be involved within the central nervous system. Furthermore, vitamin D insufficiency is widespread in temperate countries and in patients with MS at the earliest stages of the disease, suggesting that the deleterious effects related to vitamin D insufficiency may be exerted in these patients. In fact, many genetic and environmental risk factors appear to interact and contribute to MS. In genetics, several human leukocyte antigen (HLA) alleles (more particularly HLA-DRB1*1501) could favour the disease whereas some others could be protective. Some of the genes involved in vitamin D metabolism (e.g. CYP27B1) also play a significant role. Furthermore, three environmental risk factors have been identified: past Epstein-Barr virus infection, vitamin D insufficiency and cigarette smoking. Interactions between genetic and environmental risk or protective factors may occur during the mother's pregnancy and could continue during childhood and adolescence and until the disease is triggered in adulthood, therefore possibly modulating the MS risk throughout the first decades of life. Furthermore, some clinical findings already strongly suggest that vitamin D status influences the relapse rate and radiological lesions in patients with MS, although the results of adequately powered randomized clinical trials using vitamin D supplementation have not yet been reported. While awaiting these incontrovertible results, which might be long in coming, patients with MS who are currently in vitamin D insufficiency should be supplemented, at least for their general health status, using moderate doses of the vitamin.

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Section: Genetic Risk Factors For Multiple Sclerosis Possibly Involvimentioning

confidence: 99%

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Pierrot‐Deseilligny

Souberbielle

2013

Ther Adv Neurol Disord

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“…EBNA-specific antibodies in individuals who developed MS did not differ significantly from healthy controls before reaching the age of 20, while EBNA1 antibodies were two to threefold elevated in MS individuals at the age of 25 or older suggesting an age-dependent alteration in EBV-specific antibody titers. No correlation between the age nor the severity of IM infection and MS risk could be found [20,21]. Levin et al speculated that the observed changes in EBV immunity could be due to concomitant infection with other microorganisms or possibly with distinct strains of EBV that alters immune responses to the virus and lead to higher risk of MS.…”

Section: Epstein-barr Virusmentioning

confidence: 99%

Environmental triggers of multiple sclerosis

Kakalacheva

Lünemann

2011

FEBS Letters

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a b s t r a c tMultiple sclerosis is a chronic immune-mediated disease of the central nervous system that develops in young adults with a complex genetic predisposition. Similar to other autoimmune disease, HLA-DR and -DQ alleles within the HLA class II region on chromosome 6p21 are by far the strongest risk-conferring genes. Less robust susceptibility effects have been reported for non-MHC related genetic variants. Improvements in the design of epidemiological studies helped to identify consistent environmental risk-associations such as the increased susceptibility for MS in individuals with a history of infectious mononucleosis, a symptomatic primary infection with the human c-herpesvirus Epstein-Barr virus (EBV). Sun exposure and serum vitamin D levels are emerging non-infectious environmental risk factors that may have independent roles. The analysis of environmental effects will likely expand in the next few years and will allow for the generation of testable hypotheses as to how environmental insults interact with genetic factors to jointly determine the susceptibility to MS. Insights gained from these studies might facilitate the development of prevention strategies and more effective treatments for MS.

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“…This virus is widely spread amongst the population, causing latent infections with continuous exacerbations and, finally, it shows immune-modulating activity [2]. The epidemiology of infectious mononucleosis (IM) and MS [3] are also very parallel, and it has been observed that individuals who have suffered late IM present a higher risk of developing MS [4][5][6][7] and the event is preceded by an increase in the specific antibodies many years before [8][9][10]. A recent study found evidence of EBV infection in a substantial proportion of brain-infiltrating B cells and plasma cells in nearly 100% of the MS cases examined.…”

Section: Introductionmentioning

confidence: 99%

Relation between Epstein-Barr virus and multiple sclerosis: analytic study of scientific production

Santiago

Gutiérrez

Sorlózano

et al. 2010

Eur J Clin Microbiol Infect Dis

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Numerous studies have been carried out to determine whether infection by the Epstein-Barr virus (EBV) can be considered as a risk factor for multiple sclerosis (MS). This work is a meta-analysis of casecontrol observational studies published before January 2009 aimed at assessing the degree of association between EBV and MS infections. A Medline electronic database search was carried out using "Epstein-Barr virus" and "multiple sclerosis" as keywords, from which we selected 30 published studies that met our methodology criteria. We found an association between MS and an exposure to EBV, studied by determining the anti-VCA IgG antibodies (odds ratio [OR]=5.5; 95% confidence interval [CI]=3.37-8.81; p<0.0001), anti-complex EBNA IgG (OR=5.4; 95% CI= 2.94-9.76; p<0.0001) and anti-EBNA-1 IgG (OR=12.1; 95% CI=3. 13-46.89; p<0.0001). No significant association could be found when studying anti-EA IgG (OR=1.3; 95% CI=0.68-2.35; p=0.457), EBV DNA in serum (OR= 1.8; p=0.051) and DNA in brain tissues and in cerebrospinal fluid (CSF) (OR=0.9; 95% CI=0.38-2.01; p=0.768). This meta-analysis detected an association between infection by EBV and MS through the investigation of antibodies, mainly anti-EBNA-1, anticomplex EBNA and anti-VCA IgG.

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Multiple Sclerosis After Infectious Mononucleosis

Cited by 184 publications

References 21 publications

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Environmental triggers of multiple sclerosis

Relation between Epstein-Barr virus and multiple sclerosis: analytic study of scientific production

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