New blood test predicts MS risk years before symptoms appear

A team of researchers from the Medical University of Vienna has developed a blood test that can accurately identify people at risk of developing multiple sclerosis (MS) several years before the first symptoms appear. In the future, this will allow diagnostic and therapeutic measures to be carried out early enough to delay or even prevent the onset of the disease. The study was published in Nature Communications.

The new method was developed by research groups led by Elisabeth Puchhammer-Stöckl and Hannes Fitzen from the Center for Virology and Thomas Berger and Paulus Rommer from the Department of Neurology at the Medical University of Vienna. It is based on an immunological test that detects 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 being found in almost all cases of MS.

Specifically, the test detects autoantibodies, i.e. antibodies that are initially produced against a specific region of the EBV protein EBNA-1 (Epstein-Barr virus nuclear antigen 1), but also cross-react with certain structures in the human brain. These antibodies can be observed as early as three years after EBV infection – long before victims develop clinical symptoms of MS.

When these antibodies are measured repeatedly, a significantly increased risk of a subsequent MS diagnosis can be detected. “Our study shows that people who have high levels of these antibodies at least twice are more likely to develop MS in the following years,” says first author Hannes Fitzen.

The retrospective study was based on blood samples from more than 700 patients with MS and more than 5,000 controls. In part of the cohort, the researchers were able to track the initial EBV infection and then follow the development of MS over time. In this group, persistently high antibody levels were associated with a greatly increased risk of developing MS and rapid disease progression.

Multiple sclerosis can be predicted immunologically long before symptoms appear

Multiple sclerosis is a chronic inflammatory disease of the central nervous system that affects about 2.8 million people worldwide. Its development is associated with immunological processes that can be triggered by infection with the Epstein-Barr virus. Almost every person (90-95% of the population) is infected with EBV during their lifetime, and the virus remains in the body for life.

Primary infection may be asymptomatic or cause a symptomatic illness known as infectious mononucleosis. In some people, especially those who have had symptomatic illness, EBV infection can cause an abnormal immune response in which the body's own immune system attacks structures in the central nervous system.

"Our study shows that using this antibody test, the development of MS becomes immunologically predictable long before the first symptoms appear," said study leader Puchhammer-Stöckl, head of the Center for Virology at the Medical University of Vienna.

Other markers, such as neurofilament light chain (NfL) or glial fibrillary acidic protein (GFAP), which indicate damage to nerve cells, only begin to increase later in the process.

The new test could therefore become an important tool for the early identification of people at high risk of developing MS.

"This would allow these people to be diagnosed and treated so early that the onset of MS could be delayed or perhaps even prevented," added study co-leader Rommer.

“Based on our findings, we suggest screening populations at increased risk of MS, such as those who have had infectious mononucleosis,” said Berger, head of the department of neurology at the Medical University of Vienna. However, he said further research is needed before the new test can be used in clinical practice.