Broadened and Elevated Humoral Immune Response to Ebna1 in Pediatric Multiple Sclerosis

Lünemann, JD; Huppke, Peter; Roberts, Susanne; Brück, Wolfgang; Gärtner, Jutta; Münz, Christian

doi:10.1212/01.wnl.0000326576.91097.87

Cited by 70 publications

(46 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prior EBV infection is thus far the strongest and most consistent environmental factor associated with pediatric and adult‐onset MS 9, 10, 11, 12, 13, 20, 21. We observed that this association with pediatric MS is seen regardless of race and ethnicity, although the association is stronger in whites, as recently reported in adult‐onset MS 14.…”

Section: Discussionsupporting

confidence: 82%

“…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. Using a large case–control study, we aimed to assess the heterogeneity of association between remote infections with common herpesviruses and the risk of pediatric MS in children with a diverse racial and ethnic background.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Heterogeneity in association of remote herpesvirus infections and pediatric MS

Nourbakhsh

Rutatangwa

Waltz

et al. 2018

Ann Clin Transl Neurol

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Heterogeneity in association of remote herpesvirus infections and pediatric MS

Nourbakhsh

Rutatangwa

Waltz

et al. 2018

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…11 The phenomenon of epitope spreading has also been described in subjects with MS who show increased T-cell-mediated activity against a broader range of epitopes of specific antigens as compared to healthy controls. This has been described both in adults and children with MS. 35 These broadened responses to EBV antigens are specific to EBNA-1 and not seen in response to VCA. This may explain the raised total EBNA-1 IgG we see in this study (and many others) and future work to elucidate the epitopes that these antibodies are directed toward would be useful in answering this question.…”

Section: Change In Edssmentioning

confidence: 98%

Humoral immune response to EBV in multiple sclerosis is associated with disease activity on MRI

Farrell

Antony²,

Wall³

et al. 2009

Neurology

191

164

View full text Add to dashboard Cite

show abstract

“…Pediatric MS patients were also observed to have increased and broadened recognition of EBV-encoded nuclear antigen-1 (EBNA1) antibodies, pointing at an early dysregulation of virus-specific immune control [25].…”

Section: Epstein-barr Virusmentioning

confidence: 99%

Environmental triggers of multiple sclerosis

Kakalacheva

Lünemann

2011

FEBS Letters

View full text Add to dashboard Cite

a b s t r a c tMultiple sclerosis is a chronic immune-mediated disease of the central nervous system that develops in young adults with a complex genetic predisposition. Similar to other autoimmune disease, HLA-DR and -DQ alleles within the HLA class II region on chromosome 6p21 are by far the strongest risk-conferring genes. Less robust susceptibility effects have been reported for non-MHC related genetic variants. Improvements in the design of epidemiological studies helped to identify consistent environmental risk-associations such as the increased susceptibility for MS in individuals with a history of infectious mononucleosis, a symptomatic primary infection with the human c-herpesvirus Epstein-Barr virus (EBV). Sun exposure and serum vitamin D levels are emerging non-infectious environmental risk factors that may have independent roles. The analysis of environmental effects will likely expand in the next few years and will allow for the generation of testable hypotheses as to how environmental insults interact with genetic factors to jointly determine the susceptibility to MS. Insights gained from these studies might facilitate the development of prevention strategies and more effective treatments for MS.

show abstract

Broadened and Elevated Humoral Immune Response to Ebna1 in Pediatric Multiple Sclerosis

Cited by 70 publications

References 11 publications

Heterogeneity in association of remote herpesvirus infections and pediatric MS

Heterogeneity in association of remote herpesvirus infections and pediatric MS

Humoral immune response to EBV in multiple sclerosis is associated with disease activity on MRI

Environmental triggers of multiple sclerosis

Contact Info

Product

Resources

About