MS Disease-Modifying Treatments Affect Cellular Response to Epstein-Barr Virus Antigen

Testing cellular response to Epstein-Barr virus nuclear antigen-1 (EBNA-1) may benefit patients with multiple sclerosis (MS), suggests a study published in the journal Neurology: Neuroimmunology & Neuroinflammation.

“Epstein-Barr virus (EBV) has been strongly implicated in the pathogenesis of MS,” explained corresponding author Hugh Kearney, PhD, of Trinity College Dublin, Ireland, and coauthors in the study background. “Despite this, there are no routinely used tests to measure cellular response to EBV.”

For the study, researchers developed a novel test of cellular response to EBNA-1, an EBV latent antigen. Whole blood samples were stimulated with PepTivator EBNA1 peptides as well as a control virus-cytomegalovirus peptide. Investigators looked at cellular response to stimulation with interferon gamma (IFN-γ) and interleukin-2 (IL-2). Additionally, they compared cellular responses to EBNA1 with immunoglobulin G (IgG) responses to EBNA1, viral capsid antigen, and EBV viral load.

The study found a higher level of cellular response with IFN-γ in 86 patients with relapsing-remitting MS compared with healthy control subjects and people with epilepsy. Disease-modifying treatment with either anti-CD20 monoclonal antibodies or dimethyl fumarate led to cellular response similar to levels in healthy controls or people with epilepsy. Consistent with IFN-γ, patient response to IL-2 stimulation showed suppression with anti-CD20 monoclonal antibodies and dimethyl fumarate.

However, the investigation found no differential effect of disease-modifying treatment on levels of IgG to either EBNA-1 or viral capsid antigen. Meanwhile, cellular response to cytomegalovirus did not appear to differ among patients with MS, patients with epilepsy, and healthy controls.

“A methodology, such as outlined in this study, which uses whole blood samples, could potentially enhance understanding of the effect of currently available disease-modifying treatments on the cellular cell response to EBNA-1,” researchers wrote. “Furthermore, this technique has the potential to be used in future clinical trials of treatments that directly target the virus or its immune response.”

Reference

Dungan L, Dunne J, Savio M, et al. Disease-modifying treatments for multiple sclerosis affect measures of cellular immune responses to EBNA-1 peptides. Neurol Neuroimmunol Neuroinflamm. 2024;11(3):e200217. doi:10.1212/NXI.0000000000200217