EBV antibody test can predict MS years before symptom onset
Detecting EBV antibodies could allow for pre-symptom treatment, scientists say
Researchers have developed a blood test to identify people at risk of developing multiple sclerosis (MS) years before the first symptoms appear.
The test, described in a recent study, looks for antibodies against a protein of the Epstein-Barr virus (EBV), which is a leading risk factor for MS.
The study, “Early identification of individuals at risk for multiple sclerosis by quantification of EBNA-1381-452-specific antibody titers,” was published in Nature Communications.
“When using this antibody assay, the development of MS becomes immunologically predictable long before the first symptoms appear,” Elisabeth Puchhammer-Stöckl, MD, head of the Center for Virology at Medical University of Vienna (MedUni Vienna) and the study’s leader, said in a university press release.
Test would allow diagnosis, treatment at early stage
“This would allow the diagnosis and treatment of these individuals at such an early stage that the onset of MS could be delayed or perhaps even prevented,” added Paulus Rommer, MD, co-study leader and associate professor at MedUni Vienna.
MS is a neurodegenerative condition in which the body’s own immune system mistakenly attacks myelin, a fatty substance that protects and supports the function of nerve cells.
The exact causes of this autoimmune attack haven’t been pinpointed, but it likely involves a combination of genetic and environmental factors. There’s a need to identify at-risk individuals early on to enable the start of interventions to slow or prevent nerve cell death.
EBV is a very common virus that infects up to 95% of people at some point in their lives. Many people don’t experience symptoms and will never know they’ve had it, but it is also the leading cause of infectious mononucleosis, more commonly known as “mono,” or the “kissing disease.”
While most people who have had EBV don’t develop MS, virtually all people with MS have been infected with the virus. A landmark study from a few years ago found that infection with the virus raised the risk of MS by more than 30 times.
Research has since suggested that the body develops antibodies against a specific part of an EBV protein called EBNA-1, and that these antibodies then mistakenly cross-react with myelin-related proteins to drive MS.
In the study, the scientists explored whether a test to measure levels of these specific antibodies could be used as a biomarker to predict a person’s risk of developing the neurodegenerative disease.
They measured the antibodies in blood samples from more than 700 people with relapsing-remitting MS, as well as more than 5,000 people without it (a control group).
Around 98% of people with MS and 78% of the control group had detectable antibodies against the specific region of EBNA-1, with levels significantly higher in people at the time of their MS diagnosis. Among those with the neurodegenerative disease, higher antibody levels were associated with indicators of greater disease severity.
In a subgroup of individuals for whom the time of the initial EBV infection could be traced, the antibodies became detectable within three years of the infection and about five years before an MS diagnosis.
Consistently high antibody levels linked to greatest risk of developing MS later
The researchers also tested four blood samples from these participants collected between the time of infection and their MS diagnosis, with about a nine-month interval between each sample. Results showed that people who consistently had high levels of the antibodies were at the greatest risk of developing MS later on.
Specifically, high antibody levels in two or more samples over the three years after the EBV infection was observed in 96% of people who went on to develop MS and 5.6% of people who did not. This means that people with high antibody levels in at least two samples were 400 times more likely to develop MS.
“Our research shows that people in whom high levels of these antibodies are detected at least twice will likely develop MS in the following years,” said Hannes Vietzen, PhD, a postdoctoral researcher at MedUni Vienna and the study’s first author.
Consistently high antibody levels in all blood tests after EBV infection was only observed in MS patients and was also associated with a more rapid development of MS.
Importantly, these elevations in EBV antibodies were observed earlier than other biomarkers of nervous system damage that are linked to MS.
Overall, “this … biomarker allows the early, reliable, and non-invasive identification of people likely to be diagnosed with MS,” the scientists wrote, noting that this “may represent a window for early treatment to delay or even prevent conversion to clinical MS.”
The researchers are proposing the use of the test to screen at-risk populations, such as people who have had mono. However, more studies are still needed to validate the test and its predictive potential before it could be used in clinical practice.
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