Journal
JOURNAL OF AUTOIMMUNITY
Volume 106, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2019.102332
Keywords
Epstein barr virus; EBNA-1; Multiple sclerosis
Categories
Funding
- National Institute of Allergy and Infectious Diseases [U19A1082714, U01AI130830, R01A1024717]
- National Institute of Arthritis, Musculoskeletal and Skin Diseases [R01AR045451, P30AR073750]
- National Institute of General Medical Sciences [U54GM104938]
- Department of Veterans Affairs, USA [101BX001834]
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Multiple sclerosis (MS) is an autoimmune demyelinating disease with progressive neurodegeneration and complex etiology likely involving genetic and environmental factors. MS has been associated with Epstein Barr virus (EBV) infection, with patients often showing enhanced responses to EBV antigens. To determine whether abnormal EBV nuclear antigen-1 (EBNA-1) humoral immunity can serve as an initiator of autoimmune responses in MS, we investigated the fine specificities of the humoral immune response against EBNA-1 in MS patients using solid phase epitope mapping. Antibodies from MS patients recognized an EBNA-1 epitope spanning amino acids 411-426, previously unknown to be recognized specifically by untreated MS patients. Antibodies against this epitope cross-reacted to myelin basic protein (MBP). Furthermore, animals immunized with this EBNA-1 polypeptide mounted a response against MBP and developed signs of experimental autoimmune encephalitis (EAE). These data support a link between MS and EBV through antibodies that cross-react between EBV proteins and the MBP autoantigen.
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