Heterogeneity in association of remote herpesvirus infections and pediatric MS

On behalf of the US Network of Pediatric MS Centers

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: While 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. Methods: Cases 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. Results: A 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.

Original languageEnglish (US)
Pages (from-to)1222-1228
Number of pages7
JournalAnnals of Clinical and Translational Neurology
Volume5
Issue number10
DOIs
StatePublished - Oct 1 2018

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Herpesviridae Infections
Multiple Sclerosis
Pediatrics
HLA-DRB1 Chains
Virus Diseases
Human Herpesvirus 1
Viruses
Herpesviridae
Logistic Models
Human Herpesvirus 2
Viral Antigens
Capsid
Infection
Cytomegalovirus
Demography

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Heterogeneity in association of remote herpesvirus infections and pediatric MS. / On behalf of the US Network of Pediatric MS Centers.

In: Annals of Clinical and Translational Neurology, Vol. 5, No. 10, 01.10.2018, p. 1222-1228.

Research output: Contribution to journalArticle

On behalf of the US Network of Pediatric MS Centers. / Heterogeneity in association of remote herpesvirus infections and pediatric MS. In: Annals of Clinical and Translational Neurology. 2018 ; Vol. 5, No. 10. pp. 1222-1228.
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abstract = "Objective: While 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. Methods: Cases 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. Results: A 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.",
author = "{On behalf of the US Network of Pediatric MS Centers} and Bardia Nourbakhsh and Alice Rutatangwa and Michael Waltz and Mary Rensel and Manikum Moodley and Jennifer Graves and Casper, {Theron Charles} and Amy Waldman and Anita Belman and Benjamin Greenberg and Manu Goyal and Yolanda Harris and Ilana Kahn and Timothy Lotze and Soe Mar and Teri Schreiner and Gregory Aaen and Janace Hart and Jayne Ness and Jennifer Rubin and Tillema, {Jan Mendelt} and Lauren Krupp and Mark Gorman and Leslie Benson and Moses Rodriguez and Tanuja Chitnis and John Rose and Meghan Candee and Bianca Weinstock-Guttman and Xiaorong Shao and Lisa Barcellos and Judith James and Emmanuelle Waubant",
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T1 - Heterogeneity in association of remote herpesvirus infections and pediatric MS

AU - On behalf of the US Network of Pediatric MS Centers

AU - Nourbakhsh, Bardia

AU - Rutatangwa, Alice

AU - Waltz, Michael

AU - Rensel, Mary

AU - Moodley, Manikum

AU - Graves, Jennifer

AU - Casper, Theron Charles

AU - Waldman, Amy

AU - Belman, Anita

AU - Greenberg, Benjamin

AU - Goyal, Manu

AU - Harris, Yolanda

AU - Kahn, Ilana

AU - Lotze, Timothy

AU - Mar, Soe

AU - Schreiner, Teri

AU - Aaen, Gregory

AU - Hart, Janace

AU - Ness, Jayne

AU - Rubin, Jennifer

AU - Tillema, Jan Mendelt

AU - Krupp, Lauren

AU - Gorman, Mark

AU - Benson, Leslie

AU - Rodriguez, Moses

AU - Chitnis, Tanuja

AU - Rose, John

AU - Candee, Meghan

AU - Weinstock-Guttman, Bianca

AU - Shao, Xiaorong

AU - Barcellos, Lisa

AU - James, Judith

AU - Waubant, Emmanuelle

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N2 - Objective: While 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. Methods: Cases 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. Results: A 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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