High seroprevalence of Epstein–Barr virus in children with multiple sclerosis

Pohl, Daniela; Krone, Bernd; Rostásy, Kevin; Kahler, Elke; Brunner, Edgar; Lehnert, Manfred; Wagner, Hans‐Joachim; Gärtner, Jutta; Hanefeld, F

doi:10.1212/01.wnl.0000247665.94088.8d

Cited by 200 publications

(141 citation statements)

References 10 publications

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“…Prior EBV infection is thus far the strongest and most consistent environmental factor associated with pediatric and adult‐onset MS 9, 10, 11, 12, 13, 20, 21. We observed that this association with pediatric MS is seen regardless of race and ethnicity, although the association is stronger in whites, as recently reported in adult‐onset MS 14.…”

Section: Discussionsupporting

confidence: 82%

“…Although several other studies investigated the association of prior viral infections and pediatric MS risk,9, 10, 11, 12, 13 very few studies examining the risk of MS in relation to previous viral exposures and the possible interactions with age, race and ethnicity have been conducted 14. Using a large case–control study, we aimed to assess the heterogeneity of association between remote infections with common herpesviruses and the risk of pediatric MS in children with a diverse racial and ethnic background.…”

Section: Introductionmentioning

confidence: 99%

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Heterogeneity in association of remote herpesvirus infections and pediatric MS

Nourbakhsh

Rutatangwa

Waltz

et al. 2018

Ann Clin Transl Neurol

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ObjectiveWhile prior Epstein–Barr virus (EBV) infection has been consistently associated with subsequent risk of developing multiple sclerosis (MS), the association with other common herpesviruses has been more controversial. Our objectives were to determine whether remote infection with EBV and other common herpesviruses affect the susceptibility to pediatric MS and if there are interactions between genetic and demographic factors and viral infections.MethodsCases with pediatric‐onset MS or clinically isolated syndrome within 4 years of disease onset, and controls were recruited from 16 American pediatric MS centers. Logistic regression models adjusted for potential confounders assessed the association between case status and serological evidence for past infection with EBV, cytomegalovirus (CMV), Herpes Simplex viruses‐1 (HSV‐1) and ‐2. We determined the heterogeneity of the effect of viral infection on the risk of having MS according to race, ethnicity and HLA‐DRB1:1501 status.ResultsA total of 356 pediatric cases and 493 controls were recruited. In multivariable models, EBV‐viral capsid antigen (VCA) seropositivity was associated with increased odds of having MS by 7.4 times (95% CI: 4.5–12.0, P < 0.001). Seropositivity for HSV‐1 was also associated with increased odds of having MS (OR 1.54, 95% CI: 1.06–2.25, P = 0.025) but this increase was seen only in Whites (OR = 2.18, 95% CI 1.35–3.52, P < 0.001) and those negative for HLA‐DRB1*1501 (OR = 1.89, 95% CI 1.17–3.03, P = 0.009). The effect of remote EBV infection on the risk of pediatric MS depended on race and HLA‐DRB1*15:01 status.Interpretation EBV seropositivity is strongly associated with pediatric MS, as is HSV‐1 seropositivity in subjects negative for HLA‐DRB1*15:01. Our report of interactions between select viral exposures, and age, race and DRB1 status suggests a complex effect of environmental and genetic risk factors on MS development.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Heterogeneity in association of remote herpesvirus infections and pediatric MS

Nourbakhsh

Rutatangwa

Waltz

et al. 2018

Ann Clin Transl Neurol

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“…The percentage of cases positive for this determination (99-100%) was greater than among controls (81-98%), except in the study of Bray et al [23]. In work performed among paediatric subjects, there was also a higher percentage of positive cases, but with differences more accentuated than in adults [17][18][19]. The study performed by Zivadinov et al [43] was the only one in which the proportion of positive results was higher in controls than in cases.…”

Section: Anti-vca Igg Determinationmentioning

confidence: 84%

“…The study performed by Zivadinov et al [43] was the only one in which the proportion of positive results was higher in controls than in cases. The study with the highest OR was published by Pohl et al [19] and that with highest weight was published by Bray et al [23], both of which indicate the existence of an association between the virus and the disease.…”

Section: Anti-vca Igg Determinationmentioning

confidence: 97%

“…In addition, its weight was the highest among the set. All remaining studies used serum samples [4,10,19,31,42] and the proportion of seropositive patients was also higher in cases than in controls, except for the study by Banwell et al [18], which was carried out in children, and with an OR that failed to indicate any association between the virus and MS. The article with the highest OR was that by Haahr et al [4].…”

Section: Anti-ebna-1 Igg Determinationmentioning

confidence: 99%

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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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Environmental risk factors for multiple sclerosis. Part I: The role of infection

Ascherio

Munger

2007

Annals of Neurology

936

768

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Although genetic susceptibility explains the clustering of multiple sclerosis (MS) cases within families and the sharp decline in risk with increasing genetic distance, it cannot fully explain the geographic variations in MS frequency and the changes in risk that occur with migration. Epidemiological data provide some support for the "hygiene hypothesis," but with the additional proviso for a key role of Epstein-Barr virus (EBV) in determining MS risk. We show that whereas EBV stands out as the only infectious agent that can explain many of the key features of MS epidemiology, by itself the link between EBV and MS cannot explain the decline in risk among migrants from high to low MS prevalence areas. This decline implies that either EBV strains in low-risk areas have less propensity to cause MS, or that other infectious or noninfectious factors modify the host response to EBV or otherwise contribute to determine MS risk. The role of infectious factors is discussed here; in a companion article, we will examine the possible role of noninfectious factors and provide evidence that high levels of vitamin D may have a protective role, particularly during adolescence. The primary purpose of these reviews is to identify clues to the causes of MS and to evaluate the possibility of primary prevention.

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High seroprevalence of Epstein–Barr virus in children with multiple sclerosis

Cited by 200 publications

References 10 publications

Heterogeneity in association of remote herpesvirus infections and pediatric MS

Heterogeneity in association of remote herpesvirus infections and pediatric MS

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

Environmental risk factors for multiple sclerosis. Part I: The role of infection

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