Multiple Sclerosis and Epstein-Barr Virus

Abstract

Context Infection with Epstein-Barr virus (EBV) has been associated with an increased risk of multiple sclerosis (MS), but the temporal relationship remains unclear. Objective To determine whether antibodies to EBV are elevated before the onset of MS. Design, Setting, and Population Nested case-control study conducted among more than 3 million US military personnel with blood samples collected between 1988 and 2000 and stored in the Department of Defense Serum Repository. Cases were identified as individuals granted temporary or permanent disability because of MS. For each case (n=83), 2 controls matched by age, sex, race/ethnicity, and dates of blood sample collection were selected. Main Outcome Measures Antibodies including IgA against EBV viral capsid antigen (VCA) and IgG against VCA, nuclear antigens (EBNA complex, EBNA-1, and EBNA-2), diffuse and restricted early antigens, and cytomegalovirus. Results The average time between blood collection and MS onset was 4 years. The strongest predictors of MS were serum levels of IgG antibodies to VCA or EBNA complex. The risk of MS increased monotonically with these antibody titers; relative risk (RR) in persons in the highest category of VCA (Ն2560) compared with those in the lowest (Յ160) was 19.7 (95% confidence interval [CI], 2.2-174; P for trend=.004). For EBNA complex titers, the RR for those in the highest category (Ն1280) was 33.9 (95% CI, 4.1-283; P for trend Ͻ.001) vs those in the lowest category (Յ40). Similarly strong positive associations between EBV antibodies and risk of MS were already present in samples collected 5 or more years before MS onset. No association was found between cytomegalovirus antibodies and MS. Conclusion These results suggest a relationship between EBV infection and development of MS.

Breast cancer, cytomegalovirus and Epstein–Barr virus: a nested case–control study

“…The CMV and EBV antibody levels in stored blood remain stable despite prolonged storage (Jellum et al, 1993;Pappin et al, 1995;Levin et al, 2003). The study was approved by the Regional Ethics Committee of Southern Norway and Data Inspectorate, Norway.…”

Exploring the origins of grey matter damage in multiple sclerosis

“…This could be caused by an infectious organism located in the adjacent meninges or by a chronic compartmentalised inflammatory response to selfantigen(s). Several epidemiological studies have suggested that Epstein-Barr virus (EBV) is one of the strongest candidates for this infectious agent [56][57][58] and EBV proteins and RNA have been detected in B-cells in the meninges and perivascular spaces of MS cases with extensive meningeal infiltrates and cortical demyelination [59][60][61] . It has been proposed that failure to control latent EBV infection in an immune privileged site, such as the subarachnoid space, could lead to recurrent intrathecal reactivation of EBV and tissue damage in the nearby grey matter 62,63 .…”

B cells in multiple sclerosis

“…Herpesviruses-In the past decade, two human herpesviruses have also been associated with MS. One is human herpesvirus-6 (HHV-6), the cause of roseola, and the other is Epstein-Barr virus (EBV), which causes infectious mononucleosis (88)(89)(90)(91)(92). The detection of fingerprints of these two ubiquitous viruses known to be latent in blood B-(EBV) or T-(HHV-6) cells is intriguing, since the primary encounter with either virus usually occurs before or during puberty, the same time that epidemiologic evidence indicates exposure to the disease-causing agent of MS.…”