Epstein–Barr virus and Mycobacterium avium subsp. paratuberculosis peptides are cross recognized by anti-myelin basic protein antibodies in multiple sclerosis patients

• Two peptides from EBV and MAP were found to cross-react with a MBP epitope in MS.
• Competitive assay showed the possibility of a molecular mimicry mechanism.
• EBV and MAP might trigger autoimmunity through a common target.

Epstein–Barr virus and Mycobacterium avium subsp. paratuberculosis (MAP) have been associated to multiple sclerosis (MS). We searched for antibodies against the homologous peptides Epstein–Barr virus nuclear antigen 1 (EBNA1)400–413, MAP_0106c protein (MAP)121–132, and myelin basic protein (MBP)85–98 on a MS Sardinian cohort, showing that these antibodies are highly prevalent among MS patients compared to healthy controls. Competitive assay demonstrated that antibodies recognizing EBNA1400–413 and MAP121–132 cross-react with MBP85–98, possibly through a molecular mimicry mechanism. Indeed, the fact that peptides from different pathogens can be cross-recognized by antibodies targeting self-epitopes supports the hypothesis that EBV and MAP might trigger autoimmunity through a common target.