Signs of multiple sclerosis appear in the blood several years before symptoms appear.

In our country, more than 50 thousand people suffer from multiple sclerosis, the most common inflammatory disease that affects the sheaths of nerve fibers (myelin) of the central nervous system (CNS). In young people, they occupy first place among neurological disorders leading to disability.

One of the biggest challenges doctors face is that, according to the renowned Mayo Clinic, there are no specific tests for multiple sclerosis (MS). The diagnosis of this condition is based on the exclusion of other diseases that may cause similar signs and symptoms, which is called a “differential diagnosis.” This leads to delays in treatment and difficulties in improving the quality of life of patients and their families. Autoimmune diseases such as multiple sclerosis are thought to result in part from rare immune responses to common infections.

MS can cause a devastating loss of motor control, although new treatments may slow the progression of the disease and, for example, preserve a patient’s ability to walk. Obviously, the earlier the diagnosis is made, the better the prognosis.

Now, a study published in the journal Nature Medicine points to a way to speed up treatment for patients with multiple sclerosis (MS). Scientists at the University of California, San Francisco (USA), led by Michael Wilson, discovered a clue in the blood of some people who subsequently developed the disease.

In about 1 in 10 cases of multiple sclerosis, the body begins to produce a special set of antibodies against its own proteins several years before symptoms appear. These autoantibodies appear to bind to both human cells and common pathogens, possibly explaining the immunological attacks on the brain and spinal cord that are a hallmark of multiple sclerosis.

“Over the past few decades, there has been a movement in the field to treat multiple sclerosis earlier and more aggressively using new and more powerful treatments,” Wilson explains. “A diagnostic result like this makes early intervention more likely, giving patients hope for a better life.”

It all started in 2014, when Wilson joined forces with study co-author Joe DeRisi to develop better tools for identifying the culprits of autoimmune diseases. To do this, they developed a method for creating viruses that display protein fragments as flags on their surface, called phage immunoprecipitation sequencing (PhIP-Seq), and further optimized it for detecting autoantibodies in human blood.

PhIP-Seq sequencing detects autoantibodies against more than 10,000 human proteins, enough to study virtually any autoimmune disease. In 2019, they successfully used it to detect a rare autoimmune disease that appears to be caused by testicular cancer.

Because of these results, Wilson’s team suggested that the system could also identify the autoantibodies underlying immune attacks in multiple sclerosis and create new opportunities for understanding and treating the disease.

In total, blood samples from 250 patients with multiple sclerosis collected after diagnosis were analyzed, in addition to samples taken five or more years earlier. These samples were compared with samples from 250 healthy people.

The test required just one thousandth of a milliliter of blood, and from this they found that 10% of patients with multiple sclerosis had a surprising number of autoantibodies in the years before diagnosis.

A dozen autoantibodies, which have a chemical structure resembling that of common viruses, including Epstein-Barr virus (EBV), which infects more than 85% of all people and has been reported in previous studies, have been cited as one of the causes. diseases.

But these were not the only signs that there were other signs of immune warfare in the brain: Patients with these autoantibodies had increased levels of neurofilament light (Nfl), a protein that is released when neurons are destroyed. This may be caused by the immune system mistaking friendly human proteins for some viral enemy, leading to lifelong development of multiple sclerosis.

“When we analyze healthy people with our technology, they all seem unique, with their own imprint of immunological experience, like a snowflake,” says DeRisi. “When one person’s immune signature becomes similar to someone else’s and no longer looks like snowflakes, we start to suspect that something is wrong, and that’s what we found in these MS patients.”

To confirm the results, the team analyzed blood samples from patients who had neurological symptoms and many, but not all, were diagnosed with multiple sclerosis. The results were repeated: 10% of patients diagnosed with MS had the same set of autoantibodies. This shows that the system was 100% predictive of multiple sclerosis diagnosis.

“The diagnosis of multiple sclerosis is not always easy because we do not have specific biomarkers for the disease,” says Wilson. “We’re very pleased that we have something that can provide greater diagnostic confidence at an earlier stage to have a specific discussion about whether treatment should be started for each patient.”

Clearly, many questions remain about multiple sclerosis, from what triggers the immune response in some patients to how the disease develops in the remaining 90% of patients. But researchers believe they now have a clear sign that multiple sclerosis is in the making.

“Imagine if we could diagnose this condition before some patients arrive at the clinic,” concludes Steven Houser, co-author of the study. “This will increase our chances of moving from suppressing diseases to curing them.”