Epstein-Barr virus (EBV) infection has long been known as a risk factor for the development of multiple sclerosis (MS) (1). However, given its high seroprevalence in the adult population (~94%), it is difficult to design a case-control study with a large enough number of EBV-negative subjects to properly assess the strength of this association. Bjornevik et al. (2) evaluated a cohort of > 10 million individuals from the US military personnel, who underwent HIV screening every two years since enrolment and whose residual serum samples were stored in a repository and available for EBV antibodies search. They identified 801 incident MS cases and randomly matched them with 1566 healthy controls (HC). All but one MS patients were seropositive for EBV on the last sample collected before diagnosis; 97% of MS patients who were seronegative for EBV on the first sample seroconverted before MS diagnosis, compared with 57% of HC. The hazard ratio (HR) for MS patients who seroconverted compared with patients who remained seronegative was 32.4. Seroconversion preceded preclinical evidence of central nervous system pathology, evaluated by measuring serum neurofilament light chain. The Authors also assessed subjects’ serum response against ~200 viral species, and the only virus associated with MS development was EBV. This study provided very solid epidemiological evidence that EBV infection is the strongest known risk factor for the development of MS. However, more studies are needed to further elucidate the molecular mechanism of this association and its possible implications in designing preventive and therapeutic strategies.
Key Points:
- Epstein-Barr virus (EBV) infection has already been implicated in the pathogenesis of multiple sclerosis (MS), but without strong epidemiological evidence given its ubiquitous nature.
- In this large nested case-control study, EBV seroconversion strongly associated with the development of MS (hazard ratio 32.4) and preceded preclinical evidence of central nervous system damage.
- The overall antibody response to viral peptides was similar in cases and controls except for EBV, arguing that the preclinical and early clinical phases in MS are not associated with immune dysregulation affecting general susceptibility to infections.
- This study provides solid evidence that EBV infection is the strongest known risk factor for the development of MS.
- More studies are needed to find possible preventive or therapeutic implications of these findings.
References:
- Bar-Or A, Pender MP, Khanna R, et al. Epstein-Barr Virus in Multiple Sclerosis: theory and Emerging Immunotherapies. Trends Mol Med. 2020;26(3):296-310. doi:10.1016/j.molmed.2019.11.003. https://pubmed.ncbi.nlm.nih.gov/31862243/
- Bjornevik K, Cortese M, Healy BC, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 2022;375(6578):296-301. doi:10.1126/science.abj8222. https://pubmed.ncbi.nlm.nih.gov/35025605/