An altered immune response to Epstein-Barr virus in multiple sclerosis: A prospective study

Background: Elevated Epstein–Barr virus (EBV) antibody titers are risk factors for multiple sclerosis (MS), but the strength and consistency of this association are not well characterized. Objectives: The objectives of this study were to determine whether this association is confounded by vitamin D or modified by gender or race, and the usefulness of EBV nuclear antigen (EBNA) antibodies as a marker for MS. Methods: We conducted a prospective study among US military personnel. Antibody titers against EBV antigens were measured in serum samples from 222 individuals who developed MS and 444 age, sex, and race/ethnicity matched controls. Conditional logistic regression was used to estimate relative risks. Results: MS risk increased with increasing titers of anti-EBNA complex ( p < 10−9) and anti-EBNA-1 ( p = 5.8 × 10−9) titers. MS risk was 36-fold higher among individuals with anti-EBNA complex IgG titers ≥320 than among those with titers <20 (95% confidence interval [CI] 9.6–136), and 8-fold higher among those with anti-EBNA-1 ≥320 than among those with anti-EBNA-1 <20 (95% CI 2.6–23). These associations were consistent across gender and race/ethnicity groups and independent from 25-hydroxyvitamin D levels. Areas under the receiver operating characteristic (ROC) curves were 0.67 for EBNA complex and 0.65 for EBNA-1. Conclusions: Serum titers of pre-onset anti-EBNA antibodies are strong, robust markers of MS risk and could be useful in an MS risk score.

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Vitamin D status modulates the immune response to Epstein Barr virus: Synergistic effect of risk factors in multiple sclerosis

Medical Hypotheses ◽

10.1016/j.mehy.2007.04.030 ◽

2008 ◽

Vol 70 (1) ◽

pp. 66-69 ◽

Cited By ~ 43

Author(s):

Trygve Holmøy

Keyword(s):

Risk Factors ◽

Multiple Sclerosis ◽

Vitamin D ◽

Immune Response ◽

Synergistic Effect ◽

Epstein Barr Virus ◽

Vitamin D Status ◽

Barr Virus ◽

Epstein Barr

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Smoking can increase nasopharyngeal carcinoma risk by repeatedly reactivating Epstein‐Barr Virus: An analysis of a prospective study in southern China

Cancer Medicine ◽

10.1002/cam4.2083 ◽

2019 ◽

Vol 8 (5) ◽

pp. 2561-2571 ◽

Cited By ~ 4

Author(s):

Ting Hu ◽

Chu‐Yang Lin ◽

Shang‐Hang Xie ◽

Geng‐Hang Chen ◽

Yu‐Qiang Lu ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Prospective Study ◽

Epstein Barr Virus ◽

Southern China ◽

Barr Virus ◽

Epstein Barr ◽

A Prospective Study ◽

Carcinoma Risk

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The interaction between smoking and Epstein-Barr virus as multiple sclerosis risk factors may depend on age

Multiple Sclerosis Journal ◽

10.1177/1352458513507820 ◽

2013 ◽

Vol 20 (6) ◽

pp. 747-750 ◽

Cited By ~ 15

Author(s):

Jonatan Salzer ◽

Hans Stenlund ◽

Peter Sundström

Keyword(s):

Risk Factors ◽

Multiple Sclerosis ◽

Epstein Barr Virus ◽

Nuclear Antigen ◽

Positive Interaction ◽

Barr Virus ◽

Older Subjects ◽

Epstein Barr ◽

A Prospective Study ◽

Epstein Barr Nuclear Antigen

The multiple sclerosis (MS) risk factors smoking and remote Epstein-Barr virus (EBV) infection have been suggested to interact statistically, but the results are conflicting. In a prospective study on 192 MS cases and 384 matched controls, we analysed levels of cotinine as a marker of smoke exposure, and Epstein-Barr Nuclear Antigen-1 antibody reactivity. We assessed interaction on the additive and multiplicative scales, and estimated the effects of the risk factors across strata of each other. The results suggest that a negative interaction may be present in samples drawn at a young age, and a positive interaction among older subjects.

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