Common viruses associated with lower pediatric multiple sclerosis risk

E. Waubant, E. M. Mowry, L. Krupp, T. Chitnis, E. A. Yeh, N. Kuntz, J. Ness, D. Chabas, J. Strober, J. McDonald, A. Belman, M. Milazzo, M. Gorman, B. Weinstock-Guttman, M. Rodriguez, J. R. Oksenberg, J. A. James

Research output: Contribution to journalArticle

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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. Glossary: ADEM: acute disseminated encephalomyelitisCI: confidence intervalCIS: clinically isolated syndromeCMV: cytomegalovirusEBNA: Epstein-Barr nuclear antigenEBV: Epstein-Barr virusHSV: herpes simplex virusIgG: immunoglobulin GMS: multiple sclerosisNMO: neuromyelitis opticaOR: odds ratioSNP: single nucleotide polymorphismVCA: viral capsid antigen.

Original languageEnglish (US)
Pages (from-to)1989-1995
Number of pages7
JournalNeurology
Volume76
Issue number23
DOIs
StatePublished - Jun 7 2011

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Multiple Sclerosis
Pediatrics
Viruses
Human Herpesvirus 1
HLA-DRB1 Chains
Odds Ratio
Confidence Intervals
Seroepidemiologic Studies
Human Herpesvirus 4
Nuclear Antigens
Herpes Simplex
Viral Antigens
Capsid
Disease Susceptibility
Cytomegalovirus Infections
Virus Diseases
Infection
Cytomegalovirus
Immunoglobulins
Referral and Consultation

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Waubant, E., Mowry, E. M., Krupp, L., Chitnis, T., Yeh, E. A., Kuntz, N., ... James, J. A. (2011). Common viruses associated with lower pediatric multiple sclerosis risk. Neurology, 76(23), 1989-1995. https://doi.org/10.1212/WNL.0b013e31821e552a

Common viruses associated with lower pediatric multiple sclerosis risk. / Waubant, E.; Mowry, E. M.; Krupp, L.; Chitnis, T.; Yeh, E. A.; Kuntz, N.; Ness, J.; Chabas, D.; Strober, J.; McDonald, J.; Belman, A.; Milazzo, M.; Gorman, M.; Weinstock-Guttman, B.; Rodriguez, M.; Oksenberg, J. R.; James, J. A.

In: Neurology, Vol. 76, No. 23, 07.06.2011, p. 1989-1995.

Research output: Contribution to journalArticle

Waubant, E, Mowry, EM, Krupp, L, Chitnis, T, Yeh, EA, Kuntz, N, Ness, J, Chabas, D, Strober, J, McDonald, J, Belman, A, Milazzo, M, Gorman, M, Weinstock-Guttman, B, Rodriguez, M, Oksenberg, JR & James, JA 2011, 'Common viruses associated with lower pediatric multiple sclerosis risk', Neurology, vol. 76, no. 23, pp. 1989-1995. https://doi.org/10.1212/WNL.0b013e31821e552a
Waubant E, Mowry EM, Krupp L, Chitnis T, Yeh EA, Kuntz N et al. Common viruses associated with lower pediatric multiple sclerosis risk. Neurology. 2011 Jun 7;76(23):1989-1995. https://doi.org/10.1212/WNL.0b013e31821e552a
Waubant, E. ; Mowry, E. M. ; Krupp, L. ; Chitnis, T. ; Yeh, E. A. ; Kuntz, N. ; Ness, J. ; Chabas, D. ; Strober, J. ; McDonald, J. ; Belman, A. ; Milazzo, M. ; Gorman, M. ; Weinstock-Guttman, B. ; Rodriguez, M. ; Oksenberg, J. R. ; James, J. A. / Common viruses associated with lower pediatric multiple sclerosis risk. In: Neurology. 2011 ; Vol. 76, No. 23. pp. 1989-1995.
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T1 - Common viruses associated with lower pediatric multiple sclerosis risk

AU - Waubant, E.

AU - Mowry, E. M.

AU - Krupp, L.

AU - Chitnis, T.

AU - Yeh, E. A.

AU - Kuntz, N.

AU - Ness, J.

AU - Chabas, D.

AU - Strober, J.

AU - McDonald, J.

AU - Belman, A.

AU - Milazzo, M.

AU - Gorman, M.

AU - Weinstock-Guttman, B.

AU - Rodriguez, M.

AU - Oksenberg, J. R.

AU - James, J. A.

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N2 - 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. Glossary: ADEM: acute disseminated encephalomyelitisCI: confidence intervalCIS: clinically isolated syndromeCMV: cytomegalovirusEBNA: Epstein-Barr nuclear antigenEBV: Epstein-Barr virusHSV: herpes simplex virusIgG: immunoglobulin GMS: multiple sclerosisNMO: neuromyelitis opticaOR: odds ratioSNP: single nucleotide polymorphismVCA: viral capsid antigen.

AB - 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. Glossary: ADEM: acute disseminated encephalomyelitisCI: confidence intervalCIS: clinically isolated syndromeCMV: cytomegalovirusEBNA: Epstein-Barr nuclear antigenEBV: Epstein-Barr virusHSV: herpes simplex virusIgG: immunoglobulin GMS: multiple sclerosisNMO: neuromyelitis opticaOR: odds ratioSNP: single nucleotide polymorphismVCA: viral capsid antigen.

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