Antibodies against Epstein-Barr nuclear antigen (EBNA) in multiple sclerosis CSF, and two pentapeptide sequence identities between EBNA and myelin basic protein

Abstract

The Epstein-Barr virus (EBV) causes infectious mononucleosis and is linked to several disparate malignancies. Prior studies on patients with multiple sclerosis (MS) showed that 100% are EBV-seropositive and that their blood contains higher antibody titers than those of controls to both transformation and lytic cycle antigens. We performed three different assays for antibodies in CSF to three major EBV antigens from patients with MS and controls. Among 93 patients with MS, 79 (85%) had CSF that reacted with a 70 kD protein, shown to be the nuclear antigen, EBNA-1, whereas only 11 (13%) of 81 EBV-seropositive controls reacted, p less than 0.001. The CSF of all 14 MS patients, unreactive on immunoblots, contained oligoclonal bands on agarose electrophoresis. Together, the two techniques exhibit 100% sensitivity in the confirmatory diagnosis of MS. We also performed amino acid searches of the Protein Identification Resource sequence database for protein homologies to EBNA. Two pentapeptide identities were found between EBNA-1 and myelin basic protein: QKRPS and PRHRD. None of more than 32,000 other proteins in the database contained both pentapeptides. In healthy EBV-seropositive persons, the EBV-specific, MHC-restricted T lymphocytes keep the EBV-containing B lymphocytes locked in the transformed state. However, in the host genetically susceptible to MS, the same population of lymphocytes might recognize and interact with either of the two identified pentapeptides, inadvertently damaging MBP.