Association of Infectious Mononucleosis with Multiple Sclerosis

Ramagopalan, S V; Valdar, William; Dyment, David A.; DeLuca, Gabriele C.; Yee, Irene M.; Giovannoni, Gavin; Ebers, George C.; Sadovnick, A. Dessa

doi:10.1159/000201564

Cited by 88 publications

(56 citation statements)

References 72 publications

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“…(b) A meta-analysis of 14 studies of prior infectious mononucleosis and MS [4] presenting in adolescents and young adults gives a combined relative risk (RR) for MS of 2.3 (95% CI; 1.7, 3.0; p = 10 –8 ). A similar risk was obtained in a more recent large study from Canada [5] with an OR of 2.06, (95% CI; 1.71–2.48). (c) Data from a large prospective study of EBV antibodies and subsequent MS in the American Nurse Health Study which comprised a cohort of 62,439 female nurses monitored since 1976.…”

Section: Discussionsupporting

confidence: 84%

Multiple Sclerosis, Lymphoma and Nasopharyngeal Carcinoma: The Central Role of Epstein-Barr Virus?

Rolls

Giovannoni²,

Constantinescu³

et al. 2009

Eur Neurol

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Background: Multiple sclerosis (MS) and Hodgkin lymphoma (HL) share epidemiologic characteristics suggesting a possible common etiology. Epstein-Barr virus (EBV) is associated with HL, Burkitt lymphoma, some varieties of non-Hodgkin lymphoma (NHL) and nasopharyngeal carcinoma (NPC).Method:Patients were located through MS databases for (a) Barking and Havering, NE London; catchment ∼400,000; MS patient number 751, and (b) Nottingham, catchment ∼2,000,000; MS patient number 1,236. Search was undertaken for lymphoma or NPC and diagnosis of MS verified by McDonald criteria. Results: We identified five UK-born and resident patients of interest: (1) male with onset HL aged 20 years developing relapsing-remitting MS 11 years later; (2) female with severe relapsing-remitting MS whose partner developed NHL, 5 years after MS diagnosis; (3) female with secondary progressive MS beginning at age 38 years who developed NHL 25 years later; (4) female diagnosed with MS aged 19 years who developed HL 4 years later, and (5) female with hereditary motor and sensory neuropathy developing cervical cancer at the age of 32 years, NPC at 33 years, and RR MS at 36 years. Conclusion: Our study supports a possible association between MS, HL, NHL, and perhaps NPC all of which are associated with EBV infection.

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Section: Discussionsupporting

confidence: 84%

Multiple Sclerosis, Lymphoma and Nasopharyngeal Carcinoma: The Central Role of Epstein-Barr Virus?

Rolls

Giovannoni²,

Constantinescu³

et al. 2009

Eur Neurol

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“…We found five NRS that addressed risk of MS [12,14,16,20,28], and were unable to find studies reporting the risk of relapse. A total of 15,252 MS cases and 9,790 controls were included in the meta-analysis.…”

Section: Rubellamentioning

confidence: 95%

“…We found eight NRS that addressed risk of developing MS [4,[16][17][18][19][20][21][22], and one study reporting risk of relapse [23]. Of the former, four were nested case-control studies, two were case-control studies, one was a cohort study, and one was a before-and-after comparison.…”

Section: Hepatitis Bmentioning

confidence: 99%

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Immunizations and risk of multiple sclerosis: systematic review and meta-analysis

2011

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The role of vaccinations in risk of developing multiple sclerosis (MS) or in risk of relapse has not been well established. The aim of this study was to estimate the effect of immunizations on risk of developing MS in adults as well as in subsequent risk of relapse. Systematic search for publications in MEDLINE (1966-January 2011), EMBASE (1977-January 2011) and the Cochrane Central Register of Controlled Trials (CENTRAL) (1961-January 2011). Both randomized clinical trials and non-randomized studies addressing the effect of any Center for Diseases Control (CDC) recommended vaccine for children, adults or travelers and BCG on risk of MS or disease relapse were included. Two reviewers independently extracted information from articles selected using a predefined datasheet. No significant change in the risk of developing MS after vaccination was found for BCG (OR 0.96, 95% CI 0.69-1.34), Hepatitis B (OR 1.00, 95% CI 0.74-1.37), Influenza (OR 0.97, 95% CI 0.77-1.23), Measles-Mumps-Rubella (MMR) (OR 1.02, 95% CI 0.64-1.61), Polio (OR 0.87, 95% CI 0.61-1.25) and Typhoid fever (OR 1.05, 95% CI 0.72-1.53). We found decreased risk of developing MS for Diphtheria (OR 0.60, 95% CI 0.40-0.90) and Tetanus (OR 0.68, 95% CI 0.54-0.84). Influenza immunization was also associated with no change in risk of MS relapse (RR 1.24, 95% CI 0.89-1.72). Risk of developing multiple sclerosis remained unchanged after BCG, Hepatitis B, Influenza, MMR, Polio and Typhoid fever immunization, whereas diphtheria and tetanus vaccination may be associated with a decreased risk of MS. Further research is needed for the remaining vaccines.

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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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Association of Infectious Mononucleosis with Multiple Sclerosis

Cited by 88 publications

References 72 publications

Multiple Sclerosis, Lymphoma and Nasopharyngeal Carcinoma: The Central Role of Epstein-Barr Virus?

Multiple Sclerosis, Lymphoma and Nasopharyngeal Carcinoma: The Central Role of Epstein-Barr Virus?

Immunizations and risk of multiple sclerosis: systematic review and meta-analysis

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

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