EBNA1

WEDNESDAY, June 19, 2024 -- The discovery that the Epstein-Barr virus might be a major driver of multiple sclerosis has re-energized research into the autoimmune disease. Now, investigators in the U.K. and Sweden believe they might be closer to understanding how the virus, which also causes mononucleosis, might help spur MS. “The discovery of the link between Epstein-Barr Virus [EBV] and multiple sclerosis has huge implications for our understanding of autoimmune disease, but we are still beginning to reveal the mechanisms that are involved," said study senior author Dr. Graham Taylor , an associate professor of tumor immunology at the University of Birmingham in England. "Our latest study shows that following Epstein-Barr virus infection there is a great deal more immune system misdirection, or cross-reactivity, than previously thought," he explained in a university news release. Reporting recently in the journal PLOS Pathogens , Taylor and his team analyzed blood samples taken from people diagnosed with MS and compared those samples to blood taken from people who'd recently recovered from EBV-linked illness. At issue is the immune system's antibody responses to the presence of EBV. Prior research had determined that one EBV-targeted antibody found in the blood, called EBNA1, also recognizes certain proteins that appear in the central nervous system, potentially explaining how EBV could end up triggering MS-linked damage. In the new study, Taylor's group have found that EBV also seems to activate another key immune system player, T-cells. These T-cells appear to recognize certain brain proteins, pointing to another potential link to MS . These "cross-reactive" T-cells were spotted in blood samples from people with MS but also in folks without the illness, Taylor's team noted. So, differences in how such cells behave between people might help explain the EBV-MS connection, the researchers theorized. “Our detection of cross-reactive T-cells in healthy individuals suggests that it may be the ability of these cells to access the brain that is important in MS," reasoned study lead author Dr. Olivia Thomas , an assistant professor of neuroscience at the Karolinska Institute in Sweden. “We have shown that the human immune system cross-recognizes a much broader array of EBV and central nervous system proteins than previously thought, and that different patterns of cross-reactivity exist," Taylor added. "Knowing this will help identify which proteins are important in MS and may provide targets for future personalized therapies." Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

The role that Epstein-Barr Virus (EBV) plays in the development of Multiple Sclerosis may be caused a higher level of cross-reactivity, where the body's immune system binds to the wrong target, than previously thought. The role that Epstein-Barr Virus (EBV) plays in the development of multiple sclerosis (MS) may be caused a higher level of cross-reactivity, where the body's immune system binds to the wrong target, than previously thought. In a new study published in PLOS Pathogens, researchers looked at blood samples from people with multiple sclerosis, as well as healthy people infected with EBV and people recovering from glandular fever caused by recent EBV infection. The study investigated how the immune system deals with EBV infection as part of worldwide efforts to understand how this common virus can lead to the development of multiple sclerosis, following 20-years of mounting evidence showing a link between the two. While previous studies have shown that antibody responses to one EBV protein -- EBNA1 -- also recognise a small number of proteins of the central nervous system, this study found that T-cells, another important part of the immune system, that target viral proteins can also recognise brain proteins. A second important finding was that these cross-reactive T-cells can be found in people with MS but also in those without the disease. This suggests that differences in how these immune cells function may explain why some people get MS after EBV infection. Dr Graham Taylor, associate professor at the University of Birmingham and one of the corresponding authors of the study said: "The discovery of the link between Epstein-Barr Virus and Multiple Sclerosis has huge implications for our understanding of autoimmune disease, but we are still beginning to reveal the mechanisms that are involved. Our latest study shows that following Epstein-Barr virus infection there is a great deal more immune system misdirection, or cross-reactivity, than previously thought." "Our study has two main implications. First, the findings give greater weight to the idea that the link between EBV and multiple sclerosis is not due to uncontrolled virus infection in the body. Second, we have shown that the human immune system cross-recognises a much broader array of EBV and central nervous system proteins than previously thought, and that different patterns of cross-reactivity exist. "Knowing this will help identify which proteins are important in MS and may provide targets for future personalised therapies." T Cells are involved During testing of blood, the team also found evidence that cross-reactive T cells that target Epstein-Barr virus and central nervous system proteins are also present in many healthy individuals. Dr Olivia Thomas from the Karolinska Institute in Sweden and joint corresponding author of the paper said: "Our detection of cross-reactive T-cells in healthy individuals suggests that it may be the ability of these cells to access the brain that is important in MS. "Although our work shows the relationship between EBV and MS is now more complex than ever, it is important to know how far this cross-reactivity extends to fully understand the link between them."

Researchers have developed a new and unique blood test to measure the immune response to the Epstein Barr Virus (EBV) which is the leading risk factor for developing multiple sclerosis (MS). Their findings have implications for future basic research in further understanding the biology of EBV in MS, but also has the potential to be applied in clinical trials that target the virus. The test that was developed using an existing diagnostic procedure as its basis and has the potential to be applied in clinical trials that target the Epstein Barr Virus A team of research scientists at Trinity College Dublin have developed a new and unique blood test to measure the immune response to the Epstein Barr Virus (EBV) which is the leading risk factor for developing multiple sclerosis (MS). Their findings are published in the journal Neurology Neuroimmunology and Neuroinflammation and have implications for future basic research in further understanding the biology of EBV in MS, but also has the potential to be applied in clinical trials that target the virus. MS is a chronic neurological disease with no known cure. It affects approximately three million people worldwide and is the second leading cause of disability in young adults. There is a pressing need for better treatments. A range of viruses relating to MS have been studied in the past but none have had such compelling evidence as EBV. The question the team considered was why do some people have known MS have a rogue immune response to EBV, a common viral infection that is generally asymptomatic? To answer this, scientists measured the cellular response of MS patients to EBNA-1, a part of the EBV that can mimic the myelin coating of nerves which are the principal site of attack of the immune system in MS. The team found that the immune response is higher to EBNA-1 in people with MS compared to those with epilepsy, or the healthy control group. The team also showed that this cellular response is impacted by currently approved medications for MS which target the immune system, but not the virus. The immune response to EBNA-1 was found to be lower in people who are taking B cell depleting medications compared to people with MS not taking medication and the level recorded was equivalent to healthy controls. B cell depleting medications are effective for reducing MS disease activity. It is not known however, how exactly they work. Many people believe that reducing B cells reduces EBV levels, as EBV can lie dormant within B cells. The scientists do not prove this theory, but do show that the immune response to EBV in MS is equal to healthy controls when these medications are used. The team believe that this supports the need for more selective reduction in EBV rather than targeting all B cells. This is of importance as B cells play an important role in fighting infection and an unselective approach can lead to unwanted side effects. The Trinity researchers are the first team of scientists to capture the immune response to EBNA-1 using whole blood samples carried out exclusively with equipment that is used in the hospital laboratory day to day. This builds on previous research that used extensive pre-processing in research laboratories. We believe this is of importance as it shows the ability for the test to be run elsewhere and at scale without a need for new equipment or personnel. This research is important because a standard blood test that was processed in a hospital laboratory provides important information on the immune system's response to EBNA-1. This response appears to be at the heart of the pathogenesis of MS. The ability to measure this in a scalable test, that was developed using an existing diagnostic test as its basis, has implications for future basic research in further understanding the biology of EBV in MS. But the test also has the potential to be applied in clinical trials that target the virus. This would mean that there is the potential to directly measure the immune response to any potential antiviral treatments, rather than measuring MS outcome measures alone. Speaking on the potential benefits of this research, Dr Hugh Kearney, Neurologist, School of Medicine, Trinity College and lead author said: "In the short term the benefit of this research is likely to be for the research community in MS. We believe the approach adopted in this test that uses whole blood samples on a robust hospital-based platform will facilitate adoption in other centres and also replication of the results with a view towards validation. In the medium term, if validated, then this would be of benefit to researchers involved in clinical trials in MS. Long term benefits will be for people with MS, who live with a chronic neurological illness as new treatments tested in clinical trials have the potential to reduce the burden of this potentially disabling disease. The next step for our team is to develop a longitudinal study. We aim to do this by recruiting newly diagnosed people with MS and measuring this blood test before treatment has started and then repeating the blood test at an interval to show that B cell depletion directly impacts on the cellular response to EBNA-1 in MS."