Epstein-Barr virus nuclear antigen-1 B-cell epitopes in multiple sclerosis twins

Background: Compared with quantitative observations, the search for qualitative changes that may characterize the immune response to Epstein-Barr virus (EBV) in multiple sclerosis (MS) has been less intense. Objective: To examine the B-cell epitopes of antibodies against the Epstein-Barr nuclear antigen-1 (EBNA-1) and their relevance for MS, through a study in disease-discordant identical twins. Methods: We evaluated the antibodies to all unique, maximally overlapping octapeptides of EBNA-1 in 12 pairs of monozygotic (MZ) twins (9 MS-discordant, 3 healthy), 3 non-twin patients and 2 healthy subjects. All except one of the patients were untreated. The EBV serology of these individuals had been assessed in advance using commercially available and in-house enzyme-linked immunosorbent assay (ELISA) kits, including assays for antibodies against select peptides of EBNA-1: EBNA-72 (GAGGGAGAGG) and EBNA-206 (EADYFEYHQEGGPDGE). Results: The glycine-alanine rich domain of EBNA-1 was immunodominant in all subjects. Compared with healthy individuals, and similarly to what has been described in infectious mononucleosis (IM) patients, affected co-twins and non-twin patients had a significantly increased response to another EBNA-1 epitope (aa. 401-411). Conclusion: In a study that controls for confounders, our data focus an EBNA-1 specificity that may be associated with MS pathogenesis

Selective association of multiple sclerosis with infectious mononucleosis

Previous studies have suggested an association between multiple sclerosis (MS) and infectious mononucleosis (IM) but data on the exact strength of this association or its selectivity have been conflicting. In this study we have evaluated the association between MS and a variety of common childhood infections and afflictions in a large population-based case-control study involving 2877 MS cases and 2673 controls in the Netherlands. We examined the frequency of different common infections and afflictions before the age of 25 and the age at which they occurred, using a self-administered questionnaire. The Odds ratios (ORs) for the occurrence of a variety of clinically manifest common childhood infections including rubella, measles, chicken pox and mumps before the age of 25 for MS cases versus controls ranged between 1.14 and 1.42, values similar to those for irrelevant probe variables used to reveal recall bias. In contrast, the OR for clinically manifest IM in MS cases versus controls, corrected for demographic variables, was 2.22 (95% confidence interval 1.73-2.86; P < 0.001). The average age of onset of IM in the population of MS cases (16.5 years) did not differ from controls (16.8 years). Our data confirm previous much smaller studies to show that the risk for MS is significantly enhanced by prior IM, and extend those previous data by showing that this association is far stronger than with other common childhood infections or afflictions. © 2008 SAGE Publications