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Abstract
Background: Because common viruses are encountered during childhood, pediatric multiple sclerosis (MS) offers a unique opportunity to investigate the influence of these viruses on disease susceptibility and the interactions between seroprevalence and select HLA genotypes. We studied seroprevalence for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV) type 1 and HLA-DRB1*1501/1503 status as predictors of pediatric MS.
Methods: This was a retrospective analysis of prospectively collected demographic, clinical, and biologic data in subjects up to 18 years of age with early MS, control subjects seen at the same regional referral pediatric MS clinics, and additional healthy pediatric control subjects.
Results: Patients with early pediatric MS (n = 189) and pediatric control subjects (n = 66) were tested. Epstein-Barr nuclear antigen-1 seropositivity was associated with an increased odds of MS (odds ratio [OR] 3.78, 95% confidence interval [CI] 1.52–9.38, p = 0.004) in analyses adjusted for age, sex, race, ethnicity, and HLA-DRB1*1501/1503 status. In multivariate analyses including EBV status, a remote infection with CMV (OR 0.27, 95% CI 0.11–0.67, p = 0.004) was associated with a lower risk of developing MS. Although a remote infection with HSV-1 was not associated with an increased odds of MS, a strong interaction was found between HSV-1 status and HLA-DRB1 in predicting MS (p < 0.001). HSV-1 was associated with an increased risk of MS in those without a DRB1*15 allele (OR 4.11, 95% CI 1.17–14.37, p = 0.03), whereas the effect was reversed in those who were DRB1*15-positive (OR 0.07, 95% CI 0.02–0.32, p = 0.001).
Conclusions: These findings suggest that some infections with common viruses may in fact lower MS susceptibility. If this is confirmed, the pathways for risk modification remain to be elucidated.
Footnotes
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Study funding: The Pediatric MS Network, initiated and sponsored by the National Multiple Sclerosis Society, includes the following centers: University of California, San Francisco, Stony Brook, Buffalo, University of Alabama Birmingham, Harvard University, and the Mayo Clinic. Dr. Mowry has a National MS Society Sylvia Lawry Fellowship Award and an NIH K23NS067055. Dr. Waubant is also supported by the Nancy Davis Foundation. Dr. James is supported by NIH RR015577, AI082714, U19AI082714, and AR053483. Dr. Oksenberg is supported by NMSS RG2901D9/1.
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- ADEM
- acute disseminated encephalomyelitis
- CI
- confidence interval
- CIS
- clinically isolated syndrome
- CMV
- cytomegalovirus
- EBNA
- Epstein-Barr nuclear antigen
- EBV
- Epstein-Barr virus
- HSV
- herpes simplex virus
- IgG
- immunoglobulin G
- MS
- multiple sclerosis
- NMO
- neuromyelitis optica
- OR
- odds ratio
- SNP
- single nucleotide polymorphism
- VCA
- viral capsid antigen.
- Received November 3, 2010.
- Accepted February 18, 2011.
- Copyright © 2011 by AAN Enterprises, Inc.
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