New blood test predicts multiple sclerosis risk years before symptoms appear

A research team at the Medical University of Vienna has developed a blood test that allows the identification of individuals at risk for developing multiple sclerosis (MS) with a high degree of certainty years before the onset of symptoms. As a result, in the future, diagnostic and therapeutic measures could be taken early enough to delay or even prevent the onset of the disease. The research has just been published in Nature Communications.

The new method was developed by research teams led by Elisabeth Puchhammer-Stöckl and Hannes Vietzen from the Center for Virology as well as Thomas Berger and Paulus Rommer from the Department of Neurology, all at MedUni Vienna. It is based on an immunological test that identifies specific antibodies against a protein of the Epstein-Barr virus (EBV). This widespread virus is known to be a key factor in the development of multiple sclerosis, with EBV detectable in almost all cases of MS.

Specifically, the test detects autoantibodies, i.e., antibodies that have originally developed against a specific section of the EBV protein EBNA-1 (Epstein-Barr nuclear antigen 1), but which also cross-react against specific structures in the human brain. These antibodies can be observed already within three years after the EBV infection—and long before clinical symptoms of MS are observed in the affected individuals.

By repeatedly measuring these antibody levels, a significantly increased risk of a later MS diagnosis can be identified. “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,” says the study’s first author Hannes Vietzen.

The retrospective study is based on blood samples obtained from more than 700 MS patients and more than 5,000 control subjects. In a part of the cohort, it was even possible to clearly trace back to the time of the initial EBV infection and to follow up from there the development of MS over time. In this group, consistently high antibody levels were associated with a highly elevated risk for MS and a rapid development of disease.

MS immunologically predictable long before clinical symptoms

Multiple sclerosis is a chronic inflammatory disease of the central nervous system that affects about 2.8 million people worldwide. Its development is linked to immunological processes that can be triggered by infection with the Epstein-Barr virus. Almost everyone (90% to 95% of the population) becomes infected with EBV during their lifetime, with the virus persisting lifelong in the body.

The primary infection may remain asymptomatic or cause symptomatic disease, called infectious mononucleosis. In some people, especially in those with symptomatic disease, EBV infection further leads to a misdirected immune response that attacks structures of their own central nervous system.

“Our study shows that, when using this antibody assay, the development of MS becomes immunologically predictable long before the first symptoms appear,” reports study leader Puchhammer-Stöckl, Head of the Center for Virology at MedUni Vienna. Other markers such as neurofilament light chain (NfL) or glial fibrillary acidic protein (GFAP) that indicate nerve cell damage, only increase later in the process.

The new test could therefore be an important tool for the early identification of individuals who are at high risk of developing MS. “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,” adds co-study leader Rommer.

“Based on our findings, we are proposing the screening of population groups with an increased risk of MS—for example, those who have had infectious mononucleosis,” says Berger, Head of the Department of Neurology at MedUni Vienna. However, further studies are needed before the new test will be used in clinical practice.

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