TY - JOUR
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
N1 - Publisher Copyright:
© 2018 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
PY - 2018/10
Y1 - 2018/10
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85053441156&partnerID=8YFLogxK
U2 - 10.1002/acn3.636
DO - 10.1002/acn3.636
M3 - Article
AN - SCOPUS:85053441156
SN - 2328-9503
VL - 5
SP - 1222
EP - 1228
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
IS - 10
ER -