Early signs of multiple sclerosis could soon be detected by a simple blood test years before symptoms start to show.
Scientists have discovered a trace in the blood of some people who later went on to develop the debilitating autoimmune disease. They say the breakthrough could hasten treatment for thousands of patients diagnosed with multiple sclerosis, or MS, every year.
The team explained that In around one in 10 cases of MS, the body begins producing a "distinctive" set of antibodies against its own proteins years before symptoms emerge. The autoantibodies appear to bind to both human cells and common pathogens, possibly explaining the immune attacks on the brain and spinal cord that are hallmarks of MS.
Severe MS can lead to patients being wheelchair-bound, although new treatments can slow the progress of the disease and, for example, preserve the ability to walk. The University of California, San Francisco, (UCSF) research team hope the autoantibodies they have discovered will one day be detected via a simple blood test, giving patients a head start on receiving treatment.
Study senior author Professor Michael Wilson, a UCSF neurologist, said: "Over the last few decades, there's been a move in the field to treat MS earlier and more aggressively with newer, more potent therapies. A diagnostic result like this makes such early intervention more likely, giving patients hope for a better life."
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Autoimmune diseases such as MS are believed to result, in part, from rare immune reactions to common infections. In 2014, Prof Wilson joined forces with Professor Joe DeRisi to develop better ways of finding the culprits behind autoimmune disease. They took a technique in which viruses are engineered to display bits of proteins like flags on their surface, called phage display immunoprecipitation sequencing (PhIP-Seq), and improved it to screen human blood for autoantibodies.
The technique detects autoantibodies against more than 10,000 human proteins, enough to investigate nearly any autoimmune disease. They used it in 2019 to discover a rare autoimmune disease that seemed to arise from testicular cancer.
Early MS symptoms - such as dizziness, spasms, and fatigue - can resemble other conditions, and diagnosis requires careful analysis of brain MRI scans. The UCSF team believed the phage display system could reveal the autoantibodies behind the immune attacks of MS and create new opportunities to understand and treat the disease.
They joined forces with Professor Mitch Wallin, of the University of Maryland, to search for autoantibodies in the blood of people with MS. Samples were obtained from the U.S. Department of Defense Serum Repository, which stores blood taken from armed service members when they apply to join the military.
The group analysed blood from 250 MS patients collected after their diagnosis, plus samples taken five or more years earlier when they joined up. The researchers also looked at comparable blood samples from 250 healthy veterans. Using just one-thousandth of a millilitre of blood from each time point, the scientists thought they would see a jump in autoantibodies as the first symptoms of MS appeared.
Instead, they found that 10 per cent of the MS patients had a "striking abundance" of autoantibodies years before their diagnosis. The dozen or so autoantibodies all stuck to a chemical pattern that resembled one found in common viruses, including Epstein-Barr Virus (EBV), which infects more than 85 per cent of all people, yet has been flagged in previous studies as a contributing cause for MS.
Years before diagnosis, the subset of MS patients had other signs of an immune "war" in the brain. The findings, published in the journal Nature Medicine, showed that patients with the autoantibodies had elevated levels of neurofilament light (Nfl), a protein that gets released as neurons break down.
Prof DeRisi said: "When we analyse healthy people using our technology, everybody looks unique, with their own fingerprint of immunological experience, like a snowflake. It's when the immunological signature of a person looks like someone else, and they stop looking like snowflakes that we begin to suspect something is wrong, and that's what we found in these MS patients."
To confirm their findings, the team analysed blood samples from patients in the UCSF Origins study. Those patients all had neurological symptoms and many, but not all, went on to be diagnosed with MS. Again, one in 10 of the patients in the Origins study who were diagnosed with MS had the same autoantibody pattern. The pattern was 100 per cent predictive of an MS diagnosis.
Prof Wilson said: "Diagnosis is not always straightforward for MS, because we haven't had disease specific biomarkers. We're excited to have anything that can give more diagnostic certainty earlier on, to have a concrete discussion about whether to start treatment for each patient."
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The team say many questions remain about MS, but they believe they now have a definitive sign that MS is brewing. Study co-senior author Professor Stephen Hauser, director of the UCSF Weill Institute for Neurosciences, added: "Imagine if we could diagnose MS before some patients reach the clinic. It enhances our chances of moving from suppression to cure."
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