19 Mar MS: Harvard Chan Study Further Identified Serologic Response to Epstein-Barr Virus
MedicalResearch.com Interview with:
Dr. Cortese
Marianna Cortese, MD, PhD
Senior Research ScientistDepartment of Nutrition
Harvard T.H. Chan School of Public HealthBoston, MA 02115
MedicalResearch.com: What is the background for this study?
Response: In a study published in Science in 2022, we reported compelling evidence that infection with the Epstein-Barr virus is the leading cause of Multiple Sclerosis. This is a follow-up study to investigate more in depth whether the antibody response to EBV is distinct in individuals with MS compared to individuals without MS and whether there is a part of EBV that the immune response is particularly targeting. For this purpose we assessed the immune response to all protein parts (peptides) of EBV and their association with MS.
Previous studies could only look at parts of EBV and this is the first study looking at all EBV peptides. Antibodies to EBV (especially to a protein called EBNA1) are known to be overall higher in individuals with MS, so we also tested whether immune response overall or the immune response to specific EBV protein parts was more important. If the immune response to a specific EBV protein part (peptide) would be standing out or distinguishing individuals with MS, we hypothesized, it could point to a specific mechanism of how EBV may cause MS, i.e. it could point for example towards “molecular mimicry”, which is when antibodies targeting a pathogen start targeting a body-own structure (for example in the brain) which resembles the protein parts of the pathogen.
MedicalResearch.com: What are the main findings? Should patients with suspected Multiple Sclerosis be tested for EBV?
Response: We found that the immune response to EBV was overall stronger in individuals with MS but did not show a specific pattern, meaning there was not a specific protein part (peptide) within EBV to which MS patients were reacting differently than the controls. Although the immune response to a number of different peptides of EBV was associated with a higher MS risk, the higher risk was no longer present for most of these peptides after accounting for the total EBNA1 antibody level, meaning the antibody response to the latter appeared more important than the one to single peptides.
In other words, there is no strong evidence that there is a single EBV peptide that stands out as being selectively targeted in individuals with MS and could explain why they developed the disease. However, we can also not fully exclude the existence of such an MS-specifc EBV peptide based on our study conducted in a small sample and larger studies may be needed to identify if there are subgroups of patients with a specific antibody response.
We have known for a while that EBV antibody titers are higher in individuals with MS and that virtually all are positive for EBV.
The higher antibody levels could be one additional factor to consider together with other criteria as MRI or other lab results when assessing the risk of MS but we did not identify a specific “fingerprint” in the immune response that would allow to take a blood sample and identify if someone has MS or will develop MS based on specific antibodies to EBV. So in this regard it will not be useful to test MS patients for EBV.
MedicalResearch.com: What should readers take away from your report?
Response: We can not clearly identify individuals at risk of developing MS based on their immune response to EBV. The antibody response is not specific, it is however overall stronger.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: Larger studies may be needed to identify subsets of patients that react to specific EBV proteins, if these exist. Other mechanisms need to be considered and investigated to understand how EBV causes MS, which will open avenues for prevention and treatment.
Citation:
Cortese M, Leng Y, Bjornevik K, et al. Serologic Response to the Epstein-Barr Virus Peptidome and the Risk for Multiple Sclerosis. JAMA Neurol. Published online March 18, 2024. doi:10.1001/jamaneurol.2024.0272
https://jamanetwork.com/journals/jamaneurology/article-abstract/2816475
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Last Updated on March 19, 2024 by Marie Benz MD FAAD