2024-04-22 00:03:17
Early warning signs: The neurodegenerative disease multiple sclerosis is announced in some cases by characteristic autoantibodies in the blood, a study has shown. Consequently, these molecular precursors are present in the blood long before the first symptoms appear. This can make the diagnosis easier and make it possible for those affected to receive early treatment, as the neurologists report in “Nature Medicine”. However, such biomarkers are not found in all MS patients.
Multiple sclerosis (MS) is a chronic inflammatory disease Autoimmune disease, which destroys the muscle-controlling nerves in the brain and spinal cord. Almost three million people worldwide suffer from it. Those affected initially only notice general symptoms such as dizziness, cramps and fatigue. As the disease progresses, they become less able to move.
New therapeutic methods can effectively slow down the disease, but have not yet cured it. In order to prevent nerve damage as much as possible, early diagnosis and treatment are important. To date, MRI scans of the brains of those affected have been used, but these usually only allow a clear diagnosis when nerve damage is clearly visible. Researchers have therefore been working for some time with alternative methods to detect MS earlier.
When the body fights itself
A research team led by Colin Zamecnik from the University of California in San Francisco has now further developed a well-known procedure so that it can be used in multiple sclerosis. The neuroscientists used the standard immunoprecipitation technique, which uses genetically modified viruses that carry small pieces of human proteins on their surface. With this method, antibodies in a blood sample that bind to such proteins attach to the viruses and are thus detected.
These so-called autoantibodies are known to be the trigger for autoimmune diseases such as multiple sclerosis, where the immune system accidentally attacks the body’s own proteins. Scientists assume that the human proteins are similar to the common pathogens, so our immune system mistakenly identifies them as dangerous.
In their tests, Zamecnik and his colleagues used pieces of human proteins that resemble normal proteins Virus resemble, look like, resemble. This includes, among other things Epstein-Barr virus (EBV) proteins with such an appearance. Previous studies suggest that this virus can cause MS.
Blood samples from MS patients screened
Using this immunoprecipitation technique, Zamecnik 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 tested both blood samples taken shortly after an MS diagnosis and those collected on average five years earlier when they joined the military.
The researchers also compared these samples with those from 250 healthy test subjects. “A phenomenal group of individuals to see how this kind of autoimmunity develops at the onset of this disease,” says Zamecnik.
Blood markers reveal multiple sclerosis before symptoms begin
In fact, the neuroscientists found a characteristic pattern of multiple autoantibodies in the tests for multiple sclerosis. In some cases, these did not only appear at the onset of symptoms, but rather in the older blood samples. In ten percent of the MS patients examined, these immune markers were evident years before diagnosis, the team reports.
Further analysis also confirmed that there are increased levels of the protein serum neurofilament light (sNfL) in the blood of MS patients. This protein is released into the blood by nerve cells when they die, as the researchers explain. In the study, this biomarker was also found in the early blood samples, which already contained the autoantibody signature before symptoms began. This indicates an early but unnoticed onset of the disease. However, sNfL is not specific to MS, but also occurs in other neuron diseases, among others Alzheimer’s and amyotrophic lateral sclerosis (IF). This biomarker is therefore not sufficient for a clear diagnosis.
To confirm their findings, Zamecnik and his colleagues repeated the tests with additional blood and cerebrospinal fluid samples from 104 diagnosed MS patients and 22 test subjects with similar neurological symptoms. The result: The characteristic autoantibodies previously observed were again found in ten percent of the samples from MS patients. However, people with similar symptoms who did not suffer from MS did not have these antibodies.
Reliable and early diagnosis for some MS patients
The neuroscientists conclude that their method is suitable for reliable and early diagnosis of MS. “Diagnosing MS is not always easy because we haven’t had disease-specific biomarkers,” says senior author Michael Wilson of the University of California, San Francisco. – We are happy that we now have something that can provide more diagnostic certainty at an earlier stage in order to have a concrete discussion about whether treatment should start, the neurologist adds.
In the future, multiple sclerosis will therefore be able to be treated as a precaution for some affected people, even before they develop the first symptoms. “This increases our chances of going from suppression to healing,” says senior author Stephen Hauser of the University of California, San Francisco. The researchers now want to use their experimental procedure to develop a standard blood test for the clinic. “Such diagnostics make early intervention more likely and give patients hope for a better life,” says Wilson.
Follow-up studies with more test subjects will now confirm the findings and also clarify why the remaining 90 per cent of MS patients do not have any of the characteristic antibodies in their blood. The new early detection procedure is currently not suitable for them. (Naturmedicin, 2024; two: 10.1038/s41591-024-02938-3)
Source: University of California – San Francisco
22 April 2024 – Claudia Krapp
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