Multiple sclerosis: The elevated antibody response to Epstein–Barr virus primarily targets, but is not confined to, the glycine–alanine repeat of Epstein–Barr nuclear antigen-1

• Antibodies to Epstein–Barr virus (EBV) are elevated in multiple sclerosis (MS).
• We studied epitopes of EBV antibodies by a microarray containing 1465 EBV peptides.
• Reactivities to 39 EBV peptides were higher (p < 0.001) in MS than in controls.
• 17 peptides were from EBNA-1 and 13 located in the EBNA-1 glycine–alanine repeat.
• Elevated EBV antibodies in MS primarily target the EBNA-1 glycine–alanine repeat.

Patients with multiple sclerosis (MS) have elevated antibodies against Epstein–Barr virus (EBV), but data on the epitope-resolved specificity of these antibodies are scarce. Using a peptide microarray containing 1465 peptides representing 8 full-length EBV proteins, we identified higher (p < 0.001) antibody reactivities to 39 EBV-peptides in MS patients (n = 29) compared to healthy controls (n = 22). Seventeen of the 39 peptides were from EBNA-1 and 13 located within the glycine–alanine repeat of EBNA-1. Further reactivities were directed against EBNA-3, EBNA-4, EBNA-6, VP26, and LMP1. Thus, antibodies against EBV in MS patients primarily target, but are not confined to, the glycine–alanine repeat of EBNA-1.