Blood test predicts future development of MS

A research team led by the Medical University of Vienna has developed a blood test that allows the identification of individuals at risk for developing multiple sclerosis (MS) — a chronic inflammatory disease of the central nervous system — with a high degree of certainty, years before the onset of symptoms. Their research, which has been published in the journal Nature Communications, could in future enable diagnostic and therapeutic measures to be taken early enough to delay or even prevent the onset of the disease.

Development of MS is linked to immunological processes that can be triggered by infection with the Epstein–Barr virus (EBV), which is known to infect 90–95% of the population during their lifetime; the primary infection may remain asymptomatic or cause symptomatic disease, called infectious mononucleosis (aka mono, or glandular fever). In some people, especially in those with symptomatic disease, EBV infection further leads to a misdirected immune response which attacks structures of their own central nervous system.

The new method is based on an immunological test that detects autoantibodies — antibodies that have originally developed against a specific section of the EBV protein EBNA1 (Epstein–Barr nuclear antigen 1), but which also cross-react against specific structures in the human brain. These antibodies can be observed 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,” said Hannes Vietzen, first author on the study.

The retrospective study is based on blood samples obtained from over 700 MS patients and more than 5000 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.

“Our study shows that, when using this antibody assay, the development of MS becomes immunologically predictable long before the first symptoms appear,” said study leader Elisabeth 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. According to co-study leader Paulus Rommer, “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.”

“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,” said Thomas 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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