Early warning signs: The neurodegenerative disease multiple sclerosis is sometimes signaled by characteristic autoantibodies in the blood, a study shows. Accordingly, these molecular precursors are found in the blood long before the first symptoms appear. As neurologists report in “Nature Medicine,” this could facilitate diagnosis and help sufferers receive early treatment. However, such biomarkers are not found in all MS patients.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that destroys the nerves that control muscles in the brain and spinal cord. It affects nearly three million people worldwide. Sufferers initially notice only general symptoms such as dizziness, cramps and fatigue. As the disease progresses, they become less able to move.

Newer treatments can effectively reduce the disease, but not yet cure it. Early diagnosis and treatment are important to prevent nerve damage as much as possible. To date, MRI scans of victims' brains are used, but these usually only allow a clear diagnosis if nerve damage is evident. So researchers have been working for some time on alternative methods for early detection of MS.

When the body fights itself

A research team led by Colin Jamecnik of the University of California, San Francisco has now further developed the well-known process so that it can be applied to multiple sclerosis. The neuroscientists used a common immunosuppression technique that uses genetically modified viruses that carry small fragments of human proteins on their surface. With this method, antibodies in the blood sample that bind to such proteins stick to the viruses, thus making them detectable.

These so-called autoantibodies are known triggers for autoimmune diseases like multiple sclerosis, in which the immune system accidentally attacks the body's own proteins. The researchers hypothesize that human proteins are so similar to common pathogens that our immune system mistakenly identifies them as dangerous.

In their experiments, Zamecnik and his colleagues used fragments of human proteins similar to those of common viruses. Among others, Epstein-Barr virus (EBV) has proteins with this motif. Previous studies have linked this virus to MS.

Blood samples from MS patients were screened

Using this immunostaining technique, Jamecnik and his colleagues looked for matching autoantibodies in blood samples from 250 MS patients. The samples came from a biobank that collects blood from US military personnel. The neuroscientists examined both blood samples collected after an MS diagnosis and blood samples collected an average of five years earlier when entering the military.

The researchers compared these samples from 250 healthy test subjects. “It's a unique cohort of individuals to see how this type of autoimmunity develops early in the course of the disease,” Jamecnik says.

Blood markers reveal multiple sclerosis before symptoms begin

In fact, neuroscientists have identified a characteristic pattern of many autoantibodies in multiple sclerosis experiments. In some cases, these appear not only at the onset of symptoms, but also in older blood samples. In ten percent of MS patients tested, these immune markers were evident years before diagnosis, the team reports.

Further analysis confirmed increased levels of the protein serum neurofilament light (sNfL) in the blood of MS patients. As the researchers explain, this protein is released into the blood when nerve cells die. In the study, this biomarker was also detected in early blood samples, which already had an autoantibody signature before the onset of symptoms. This indicates an early but unnoticed onset of the disease. However, sNfL is not specific to MS, but also occurs in other neurodegenerative diseases including Alzheimer's and amyotrophic lateral sclerosis (ALS). This biomarker is insufficient for a clear diagnosis.

To confirm their findings, Zamecnik and his colleagues repeated the experiments with additional blood and cerebrospinal fluid samples from 104 diagnosed MS patients and 22 test subjects with similar neurological symptoms. Conclusion: The previously observed characteristic autoantibodies were again observed in ten percent of samples from MS patients. However, people with similar symptoms who do not suffer from MS do not have these antibodies.

A reliable and early diagnosis for some MS patients

The neuroscientists conclude that their method is reliable and suitable for early detection of MS. “Diagnosing MS is not always easy,” said senior author Michael Wilson of the University of California, San Francisco. “We're excited that we now have something that can provide diagnostic certainty at an earlier stage to have a definitive discussion about whether treatment should be initiated,” says the neurologist.

In the future, some people with multiple sclerosis may be treated as a preventive measure before they develop the first symptoms. “This increases the chances of recovery from repression,” says senior author Stephen Houser of the University of California, San Francisco. The researchers now want to use their test method to develop a standard blood test for the clinic. “Diagnoses like this increase early intervention and give patients hope for a better life,” says Wilson.

Follow-up studies with more test subjects must now confirm the findings and clarify why the remaining 90 percent of MS patients have no characteristic antibodies in their blood. The new early detection procedure is currently not suitable for them. (Natural Medicine, 2024; Two: 10.1038/s41591-024-02938-3)

Quelle: University of California – San Francisco

22 April 2024 – Claudia Crabb