Researchers at UC San Francisco have discovered a distinct set of antibodies in the blood of some individuals who later developed multiple sclerosis (MS), potentially paving the way for earlier diagnosis and treatment of the disease. The findings, published in Nature Medicine on April 19, suggest that a simple blood test could one day help identify patients at risk of MS years before symptoms emerge.
Autoantibodies: A Harbinger of MS
The study found that in about 1 in 10 cases of MS, the body begins producing a unique set of antibodies against its own proteins years before the onset of symptoms. These autoantibodies appear to bind to both human cells and common pathogens, possibly explaining the immune attacks on the brain and spinal cord that characterize MS.
“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,” said UCSF neurologist Michael Wilson, MD, a senior author of the paper. “A diagnostic result like this makes such early intervention more likely, giving patients hope for a better life.”
Linking Infections with Autoimmune Disease
Autoimmune diseases like MS are believed to result, in part, from rare immune reactions to common infections. The researchers used a technique called phage display immunoprecipitation sequencing (PhIP-Seq) to screen human blood for autoantibodies against more than 10,000 human proteins. They analyzed blood samples from 250 MS patients collected after their diagnosis, as well as samples taken five or more years earlier when they joined the military, and compared them to samples from 250 healthy veterans.
A Consistent Signature of MS
The scientists found that 10% of the MS patients had a striking abundance of autoantibodies years before their diagnosis. These autoantibodies all stuck to a chemical pattern that resembled one found in common viruses, including Epstein-Barr Virus (EBV), which has been flagged in previous studies as a contributing cause for MS.
“When we analyze healthy people using our technology, everybody looks unique, with their own fingerprint of immunological experience, like a snowflake,” said Joe DeRisi, PhD, president of the Chan Zuckerberg Biohub SF and a senior author of the paper. “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.”
A Test to Speed Patients Toward the Right Therapies
The researchers confirmed their findings using blood samples from patients in the UCSF ORIGINS study. The autoantibody pattern was 100% predictive of an MS diagnosis. The discovery of this definitive sign that MS is brewing could lead to earlier diagnosis and treatment for patients.
“Diagnosis is not always straightforward for MS, because we haven’t had disease specific biomarkers,” Wilson said. “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.”
