Systematic Review and Meta-Analysis of the Sero-Epidemiological Association between Epstein Barr Virus and Multiple Sclerosis

AbstractBackgroundEBV infection is thought to play a central role in the development of Multiple Sclerosis (MS). If causal, it represents a target for interventions to reduce MS risk.ObjectiveTo examine the evidence for interaction between EBV and other risk factors, and explore mechanisms via which EBV infection may influence MS risk.MethodsPubmed was searched using the terms “multiple sclerosis” AND “Epstein Barr virus”, “multiple sclerosis” AND EBV, “clinically isolated syndrome” AND “Epstein Barr virus” and “clinically isolated syndrome” AND EBV. All abstracts were reviewed for possible inclusion.Results262 full-text papers were reviewed. There was evidence of interaction on the additive scale between anti-EBV antibody titre and HLA genotype (AP 0.48, p<1×10−4; RERI 3.84, p<5×10−3; S 1.68, p=0.06). Previous IM was associated with increased OR of MS in HLA-DRB1*1501 positive but not HLA-DRB1*1501 negative persons. Smoking was associated with a greater risk of MS in those with high anti-EBV antibodies (OR 2.76) but not low anti-EBV antibodies (OR 1.16). No interaction between EBV and risk factors was found on a multiplicative scale.ConclusionsEBV appears to interact with at least some established MS risk factors. The mechanism via which EBV influences MS risk remains unknown.

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CpG Island Methylator Phenotype, Helicobacter pylori, Epstein-Barr Virus, and Microsatellite Instability and Prognosis in Gastric Cancer: A Systematic Review and Meta-Analysis

PLoS ONE ◽

10.1371/journal.pone.0086097 ◽

2014 ◽

Vol 9 (1) ◽

pp. e86097 ◽

Cited By ~ 23

Author(s):

Liang Zong ◽

Yasuyuki Seto

Keyword(s):

Gastric Cancer ◽

Systematic Review ◽

Helicobacter Pylori ◽

Epstein Barr Virus ◽

Cpg Island ◽

Meta Analysis ◽

Cpg Island Methylator Phenotype ◽

Barr Virus ◽

Epstein Barr ◽

Methylator Phenotype

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Assessing the potential association between Epstein-Barr virus and oral squamous cell carcinoma: a systematic review and meta- analysis

Translational Cancer Research ◽

10.21037/tcr.2020.01.09 ◽

2020 ◽

Vol 9 (4) ◽

pp. 3092-3100 ◽

Cited By ~ 1

Author(s):

Shivaranjhany Sivakumar ◽

Archana A. Gupta ◽

Nik Mohd Mazuan Nik Mohd Rosdy ◽

Annapurny Venkiteswaran ◽

A. Thirumal Raj ◽

...

Keyword(s):

Systematic Review ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Epstein Barr Virus ◽

Meta Analysis ◽

Barr Virus ◽

Potential Association ◽

Epstein Barr

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Genetic loci for Epstein-Barr virus nuclear antigen-1 are associated with risk of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458515626598 ◽

2016 ◽

Vol 22 (13) ◽

pp. 1655-1664 ◽

Cited By ~ 25

Author(s):

Yuan Zhou ◽

Gu Zhu ◽

Jac C Charlesworth ◽

Steve Simpson ◽

Rohina Rubicz ◽

...

Keyword(s):

Multiple Sclerosis ◽

Genetic Risk ◽

Epstein Barr Virus ◽

Meta Analysis ◽

Nuclear Antigen ◽

Genetic Loci ◽

Polygenic Risk ◽

Barr Virus ◽

Genome Wide ◽

Epstein Barr

Background: Infection with the Epstein-Barr virus (EBV) is associated with an increased risk of multiple sclerosis (MS). Objective: We sought genetic loci influencing EBV nuclear antigen-1 (EBNA-1) IgG titers and hypothesized that they may play a role in MS risk. Methods: We performed a genome-wide association study (GWAS) of anti-EBNA-1 IgG titers in 3599 individuals from an unselected twin family cohort, followed by a meta-analysis with data from an independent EBNA-1 GWAS. We then examined the shared polygenic risk between the EBNA-1 GWAS (effective sample size ( Neff) = 5555) and a large MS GWAS ( Neff = 15,231). Results: We identified one locus of strong association within the human leukocyte antigen (HLA) region, of which the most significantly associated genotyped single nucleotide polymorphism (SNP) was rs2516049 ( p = 4.11 × 10−9). A meta-analysis including data from another EBNA-1 GWAS in a cohort of Mexican-American families confirmed that rs2516049 remained the most significantly associated SNP ( p = 3.32 × 10−20). By examining the shared polygenic risk, we show that the genetic risk for elevated anti-EBNA-1 titers is positively correlated with the development of MS, and that elevated EBNA-1 titers are not an epiphenomena secondary to MS. In the joint meta-analysis of EBNA-1 titers and MS, loci at 1p22.1, 3p24.1, 3q13.33, and 10p15.1 reached genome-wide significance ( p < 5 × 10−8). Conclusions: Our results suggest that apart from the confirmed HLA region, the association of anti-EBNA-1 IgG titer with MS risk is also mediated through non-HLA genes, and that studies aimed at identifying genetic loci influencing EBNA immune response provides a novel opportunity to identify new and characterize existing genetic risk factors for MS.

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Prevalence of Epstein–Barr virus antibodies in different age groups in Europe and Asia: a systematic review and meta-analysis

Health Care of the Russian Federation ◽

10.47470/0044-197x-2021-65-3-276-286 ◽

2021 ◽

Vol 65 (3) ◽

pp. 276-286

Author(s):

Tatyana V. Solomay ◽

Tatyana A. Semenenko ◽

Alexey I. Blokh

Keyword(s):

Systematic Review ◽

Growth Rate ◽

Epstein Barr Virus ◽

Meta Analysis ◽

Age Groups ◽

Maximum Growth ◽

Small Samples ◽

Barr Virus ◽

Cochrane Reviews ◽

Epstein Barr

Introduction. Attempts to assess the prevalence of antibodies (seroprevalence) to the Epstein-Barr virus have been made several times. Still, a complete understanding of this issue has not been reached due to the small samples of the surveyed. The goal is to evaluate seroprevalence in different age groups in Europe and Asia using a systematic review and meta-analysis. Material and methods. The search for publications was carried out on PubMed, Cochrane Reviews/CochraneLibrary, eLibrary, Cyberleninka, Researchgate from May 6 to 30, 2020. A total of 2,364 articles were found, 12 of which were included in the study. Seroprevalence to Epstein-Barr virus was determined in 67,561 individuals aged 0 to 80 years. The research results were distributed by age groups, continents (Europe and Asia), and their implementation (2000-2012 and 2013-2019) and subjected to meta-analysis. Results. Minimal seroprevalence was detected among children under 1 and 1-2 years of age (53.3 and 50.9%). With increasing age, it grew, and people over 18 years of age were more than 90%. In 2013-2019, the index value (68.9%) was significantly higher than in 2000-2012 (89.6%). In Asian countries in 2000-2019, seroprevalence (86.7%) was considerably higher than in Europe (76.3%). The highest growth rate was observed in 7-14 years. In 2000-2012, the maximum growth rate of seroprevalence occurred in 15-17 years and 2013-2019 - 3-6 years. For all age groups, the growth rate was higher in Europe than in Asia and 2013-2019 compared to 2000-2012. Conclusion. The meta-analysis revealed differences in seroprevalence depending on age and territory of residence and the growth of indices in the trend.

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