Antibodies to specific EBNA-1 domains and HLA DRB1*1501 interact as risk factors for multiple sclerosis.
Epitope reactivity of multiple sclerosis (MS) plasma antibodies against the Epstein-Barr virus protein EBNA-1 and its association with HLA DRB1*1501 status was investigated in a case-referent study. Based on EBNA-1 fragment reactivity and the effect of peptide blocking, four 29-36 amino acid long EBNA-1 fragments were selected for detailed studies. MS cases had increased antibody reactivity against several EBNA-1 domains, of which antibodies against EBNA-1 (amino acid 385-420) in HLA DRB1*1501 positive individuals were associated with a 24-fold risk increase for MS. The data need confirmation in a larger sample but suggest a role for this epitope in the autoimmune pathogenesis of MS.
Sundström
Peter
P
Department of Neurology, Umeå University Hospital, SE-901 85 Umeå, Sweden. peter.sundstrom@neuro.umu.se
Nyström
Maria
M
Ruuth
Kristina
K
Lundgren
Erik
E
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000378:metabolism*; D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D012307:Risk Factors
D000914:Antibodies, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D010446:Peptide Fragments; C417029:EBV-encoded nuclear antigen 1