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J Autoimmun. 2019 Sep 9:102332. doi: 10.1016/j.jaut.2019.102332. [Epub ahead of print]

Epstein Barr virus nuclear antigen 1 (EBNA-1) peptides recognized by adult multiple sclerosis patient sera induce neurologic symptoms in a murine model.

Author information

1
Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
2
Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
3
Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
4
Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
5
Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Department of Veterans Affairs VA Medical Center, Cincinnati, OH, USA.
6
Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: Judith-James@omrf.org.

Abstract

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.

KEYWORDS:

EBNA-1; Epstein barr virus; Multiple sclerosis

PMID:
31515129
DOI:
10.1016/j.jaut.2019.102332

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