Gene–environment interactions: Epstein–Barr virus infection and risk of pediatric-onset multiple sclerosis

Background and Objective: Prior Epstein–Barr virus (EBV) infection is associated with an increased risk of pediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (MS). It has been challenging to elucidate the biological mechanisms underlying this association. We examined the in...

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Bibliographic Details
Published in:Multiple sclerosis 2024-03, Vol.30 (3), p.308-315
Main Authors: Ziaei, Amin, Solomon, Olivia, Casper, T Charles, Waltz, Michael, Weinstock-Guttman, Bianca, Aaen, Greg, Wheeler, Yolanda, Graves, Jennifer, Benson, Leslie, Gorman, Mark, Rensel, Mary, Mar, Soe, Lotze, Tim, Greenberg, Benjamin, Chitnis, Tanuja, Waldman, Amy T, Krupp, Lauren, James, Judith A, Hart, Janace, Barcellos, Lisa F, Waubant, Emmanuelle
Format: Article
Language:English
Subjects:
Adult
Alleles
Antibodies
Antigen-presenting cells
Antigens
CD86 antigen
Child
Children
Drb1 protein
Epstein-Barr virus
Epstein-Barr Virus Infections - complications
Genotypes
Herpesvirus 4, Human
Histocompatibility antigen HLA
HLA-DRB1 Chains - genetics
Humans
Infections
Multiple Sclerosis
Pediatrics
Regression analysis
Risk Factors
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Summary:Background and Objective: Prior Epstein–Barr virus (EBV) infection is associated with an increased risk of pediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (MS). It has been challenging to elucidate the biological mechanisms underlying this association. We examined the interactions between candidate human leukocyte antigen (HLA) and non-HLA variants and childhood EBV infection as it may provide mechanistic insights into EBV-associated MS. Methods: Cases and controls were enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers. Participants were categorized as seropositive and seronegative for EBV-viral capsid antigen (VCA). The association between prior EBV infection and having POMS was estimated with logistic regression. Interactions between EBV serostatus, major HLA MS risk factors, and non-HLA POMS risk variants associated with response to EBV infection were also evaluated with logistic regression. Models were adjusted for sex, age, genetic ancestry, and the mother’s education. Additive interactions were calculated using relative risk due to interaction (RERI) and attributable proportions (APs). Results: A total of 473 POMS cases and 702 controls contributed to the analyses. Anti-VCA seropositivity was significantly higher in POMS cases compared to controls (94.6% vs 60.7%, p 
ISSN:1352-4585
1477-0970
DOI:10.1177/13524585231224685