Common viruses associated with lower pediatric multiple sclerosis risk

Waubant, Emmanuelle; Mowry, Ellen M.; Krupp, Lauren; Chitnis, Tanuja; Yeh, E. Ann; Kuntz, Nancy L.; Ness, Jayne; Chabas, Dorothée; Strober, Jonathan B.; McDonald, Jamie; Belman, Anita; Milazzo, Maria; Gorman, Mark; Weinstock‐Guttman, B.; Rodriguez, Moses; Oksenberg, Jorge R.; James, Judith A.

doi:10.1212/wnl.0b013e31821e552a

Cited by 134 publications

(133 citation statements)

References 29 publications

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Section: Discussionsupporting

confidence: 93%

“…This is in line with a prior report in adults26 but in contrast with two others in children 4, 27. Two small groups of controls were used in our former study which could explain differences in the findings 4. One control group included subjects with inflammatory neurological diseases while the other was recruited during a different time period and from different sites compared with cases.…”

Section: Discussionsupporting

confidence: 93%

“…In this study, HSV infection was modestly associated with MS risk according, especially in whites raising the possibility that the disparity between previous reports might be related to the racial make‐up of study populations. We also confirm an interaction between HLA‐DRB1 status and HSV infection and the risk of MS 4. Although DRB1 is more frequent in whites, a remote HSV infection was associated with increased MS risk only in HLA‐DRB1 * 15:01 negative subjects, which is the reverse interaction we identified for prior EBV infection.…”

Section: Discussionsupporting

confidence: 73%

“…We have reported the association between prior exposure to several herpesviruses and MS susceptibility in pediatric MS4 and suggested evidence for an interaction between HLA‐DRB1*15:01 status and HSV‐1. Although several other studies investigated the association of prior viral infections and pediatric MS risk,9, 10, 11, 12, 13 very few studies examining the risk of MS in relation to previous viral exposures and the possible interactions with age, race and ethnicity have been conducted 14.…”

Section: Introductionmentioning

confidence: 89%

“…The most well‐studied ones include Epstein–Barr virus (EBV), cytomegalovirus (CMV) and Herpes Simplex virus (HSV). While prior infection with EBV is reported in most patients with adult or pediatric‐onset MS,1 a few studies have suggested that remote CMV exposure might decrease the risk of having MS 3, 4…”

Section: Introductionmentioning

confidence: 99%

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Heterogeneity in association of remote herpesvirus infections and pediatric MS

Nourbakhsh

Rutatangwa

Waltz

et al. 2018

Ann Clin Transl Neurol

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ObjectiveWhile 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.MethodsCases 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.ResultsA 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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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Heterogeneity in association of remote herpesvirus infections and pediatric MS

Nourbakhsh

Rutatangwa

Waltz

et al. 2018

Ann Clin Transl Neurol

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Vaccines and the Risk of Multiple Sclerosis and Other Central Nervous System Demyelinating Diseases

et al. 2014

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IMPORTANCE Because vaccinations are common, even a small increased risk of multiple sclerosis (MS) or other acquired central nervous system demyelinating syndromes (CNS ADS) could have a significant effect on public health. OBJECTIVE To determine whether vaccines, particularly those for hepatitis B (HepB) and human papillomavirus (HPV), increase the risk of MS or other CNS ADS. DESIGN, SETTING, AND PARTICIPANTS A nested case-control study was conducted using data obtained from the complete electronic health records of Kaiser Permanente Southern California (KPSC) members. Cases were identified through the KPSC CNS ADS cohort between 2008 and 2011, which included extensive review of medical records by an MS specialist. Five controls per case were matched on age, sex, and zip code. EXPOSURES Vaccination of any type (particularly HepB and HPV) identified through the electronic vaccination records system. MAIN OUTCOMES AND MEASURES All forms of CNS ADS were analyzed using conditional logistic regression adjusted for race/ethnicity, health care utilization, comorbid diseases, and infectious illnesses before symptom onset. RESULTS We identified 780 incident cases of CNS ADS and 3885 controls; 92 cases and 459 controls were females aged 9 to 26 years, which is the indicated age range for HPV vaccination. There were no associations between HepB vaccination (odds ratio [OR], 1.12; 95% CI, 0.72-1.73), HPV vaccination (OR, 1.05; 95% CI, 0.62-1.78), or any vaccination (OR, 1.03; 95% CI, 0.86-1.22) and the risk of CNS ADS up to 3 years later. Vaccination of any type was associated with an increased risk of CNS ADS onset within the first 30 days after vaccination only in younger (<50 years) individuals (OR, 2.32; 95% CI, 1.18-4.57). CONCLUSIONS AND RELEVANCE We found no longer-term association of vaccines with MS or any other CNS ADS, which argues against a causal association. The short-term increase in risk suggests that vaccines may accelerate the transition from subclinical to overt autoimmunity in patients with existing disease. Our findings support clinical anecdotes of CNS ADS symptom onset shortly after vaccination but do not suggest a need for a change in vaccine policy.

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