Researchers detailed several pathways through which the Epstein-Barr virus may trigger and potentiate autoimmune diseases, according to a review.
In the study, published in Nature Reviews Rheumatology, the researchers documented that patients with systemic lupus erythematosus (SLE), Sjögren's syndrome, rheumatoid arthritis (RA), and multiple sclerosis demonstrated increased Epstein-Barr virus (EBV) infection rates, impaired immune control of the virus, elevated EBNA1-specific antibody titers, and higher viral reactivation compared with healthy individuals.
The researchers identified five key mechanisms:
- Molecular mimicry between EBV nuclear antigen 1 (EBNA1) and human autoantigens
- EBV-mediated B-cell reprogramming
- Dysregulation of autoimmune susceptibility genes by the EBV transcription factor EBNA2
- Insufficient host immune responses against EBV
- Viral lytic reactivation cycles.
Initial evidence indicated specific autoimmune-promoting EBV strains existed, similar to known cancer-promoting strains. The researchers noted that while EBV infected more than 95% of adults globally, just a small proportion developed autoimmune conditions.
The review discussed several therapeutic approaches under investigation:
- B-cell depletion strategies targeting EBV-positive B cells
- Development of preventive and therapeutic EBV vaccines
- Small molecule inhibitors of EBV lytic replication and latent infection.
The researchers noted that technical challenges remained as a result of the low frequency of EBV-positive B cells in patients with autoimmune diseases.
Conflict of interest declarations can be found in the study.