High Epstein-Barr antibody levels over time may aid MS diagnosis
Study points to potential way to distinguish MS from other conditions
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Viruses and antibodies.
- Persistently high Epstein-Barr virus antibody levels are common in MS patients.
- Serial EBV antibody testing can help differentiate MS from other diseases.
- This biomarker is crucial for accurate diagnosis and treatment selection.
Most people with multiple sclerosis (MS) have persistently high levels of antibodies against Epstein-Barr virus (EBV), but these antibodies are much less common in people with other neuroinflammatory diseases and in healthy people, a study found
“This study indicates that serial testing for EBV-specific antibodies could serve as an additional biomarker to help distinguish MS from other neuroinflammatory diseases that may have similar clinical and [imaging] features,” study co-author Bianca Weinstock-Guttman, MD, a professor at the University at Buffalo, said in a university news story.
The study, “Epstein-Barr virus antibodies to differentiate multiple sclerosis from other neuroinflammatory diseases,” was published in JAMA Neurology.
EBV is best known for causing infectious mononucleosis. Most adults worldwide have been infected with the virus, usually without obvious symptoms or associated with nonspecific childhood illnesses.
A large body of evidence has shown that infection with EBV is a key risk factor for developing MS, though the mechanisms underlying this association are not fully understood.
Differentiating MS from other inflammatory conditions
In MS, inflammation damages the brain and spinal cord. But inflammatory damage to the nervous system is also a hallmark of other diseases, such as myelin oligodendrocyte glycoprotein-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD), which can cause similar symptoms and may be difficult to distinguish.
Telling the difference between these diseases is absolutely crucial because they require different treatments; in fact, some approved MS treatments can cause NMOSD to worsen.
Because EBV is linked to MS but not these other diseases, scientists tested whether antibodies targeting an EBV protein called EBNA-1 might serve as a useful marker to distinguish these diseases. The study involved data on roughly 2,000 people with neurological diseases and a similar number of healthy controls.
The researchers found that MS patients frequently had high levels of EBV-targeting antibodies at the time they were diagnosed. High levels of these antibodies at the time of diagnosis were less common for people with MOGAD or NMOSD. However, they were still seen in some people with these diseases, suggesting that antibody levels at diagnosis aren’t a surefire biomarker.
The researchers then used data from a subset of individuals with multiple blood samples to determine whether MS patients tended to have high antibody levels that persisted over time.
In this analysis, almost all (96%) MS patients had high anti-EBV antibody levels in at least two of four samples collected over time. In contrast, in people with NMOSD or MOGAD, antibody levels tended to be lower over the long term: only 7.7% of patients with MOGAD and 18% of those with NMOSD had high levels in at least two of four samples.
Statistically, that means someone with high levels on multiple samples is more than 100 times more likely to have MS than these other diseases.
High levels in three or four samples were reported only in MS patients, the researchers said.
Overall, the data support the idea that persistently high levels of antibodies against EBV might be a useful diagnostic marker for distinguishing MS from other neuroinflammatory diseases, the researchers concluded.
They noted that the test is not foolproof, and high antibody levels “do not establish a diagnosis but may inform clinical judgment in diagnostically uncertain cases.”
