Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis.

Thomas OG, Bronge M, Tengvall K, Akpinar B, Nilsson OB, Holmgren E, Hessa T, Gafvelin G, Khademi M, Alfredsson L, Martin R, Guerreiro-Cacais AO, Grönlund H, Olsson T, Kockum I

Sci Adv 9 (20) eadg3032 [2023-05-19; online 2023-05-17]

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, for which and Epstein-Barr virus (EBV) infection is a likely prerequisite. Due to the homology between Epstein-Barr nuclear antigen 1 (EBNA1) and alpha-crystallin B (CRYAB), we examined antibody reactivity to EBNA1 and CRYAB peptide libraries in 713 persons with MS (pwMS) and 722 matched controls (Con). Antibody response to CRYAB amino acids 7 to 16 was associated with MS (OR = 2.0), and combination of high EBNA1 responses with CRYAB positivity markedly increased disease risk (OR = 9.0). Blocking experiments revealed antibody cross-reactivity between the homologous EBNA1 and CRYAB epitopes. Evidence for T cell cross-reactivity was obtained in mice between EBNA1 and CRYAB, and increased CRYAB and EBNA1 CD4+ T cell responses were detected in natalizumab-treated pwMS. This study provides evidence for antibody cross-reactivity between EBNA1 and CRYAB and points to a similar cross-reactivity in T cells, further demonstrating the role of EBV adaptive immune responses in MS development.

Autoimmunity and Serology Profiling [Service]

PubMed 37196088

DOI 10.1126/sciadv.adg3032

Crossref 10.1126/sciadv.adg3032

pmc: PMC10191428

Publications 9.5.0