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

Abstract

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.