UCSF scientists clear a potential path toward earlier treatment for a disease that affects nearly 1,000,000 people in the United States.
In a discovery that could hasten treatment for patients with multiple sclerosis (MS), UC San Francisco scientists have discovered a harbinger in the blood of some people who later went on to develop the disease.
In about 1 in 10 cases of MS, the body begins producing a distinctive set of antibodies against its own proteins years before symptoms emerge. These autoantibodies appear to bind to both human cells and common pathogens, possibly explaining the immune attacks on the brain and spinal cord that are the hallmark of MS.
The findings were published in Nature Medicine on April 19.
MS can lead to a devastating loss of motor control, although new treatments can slow the progress of the disease and, for example, preserve a patient’s ability to walk. The scientists hope the autoantibodies they have discovered will one day be detected with a simple blood test, giving patients a head start on receiving treatment.
“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.”
A diagnostic result like this makes such early intervention more likely, giving patients hope for a better life.”
MICHAEL WILSON, MDSenior author of the paper
Linking infections with autoimmune disease
Autoimmune diseases like MS are believed to result, in part, from rare immune reactions to common infections.
In 2014, Wilson joined forces with Joe DeRisi, PhD, president of the Chan Zuckerberg Biohub SF and a senior author of the paper, to develop better tools for unmasking 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 further optimized it to screen human blood for autoantibodies.
PhIP-Seq detects autoantibodies against more than 10,000 human proteins, enough to investigate nearly any autoimmune disease. In 2019, they successfully used it to discover a rare autoimmune disease that seemed to arise from testicular cancer.
MS affects more than 900,000 people in the US. Its early symptoms, like dizziness, spasms, and fatigue, can resemble other conditions, and diagnosis requires careful analysis of brain MRI scans.
The phage display system, the scientists reasoned, could reveal the autoantibodies behind the immune attacks of MS and create new opportunities to understand and treat the disease.
The project was spearheaded by first co-authors Colin Zamecnik, PhD, a postdoctoral researcher in DeRisi’s and Wilson’s labs; and Gavin Sowa, MD, MS, former UCSF medical student and now internal medicine resident at Northwestern University.
They partnered with Mitch Wallin, MD, MPH, from the University of Maryland and a senior author of the paper, to search for autoantibodies in the blood of people with MS. These 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 analyzed blood from 250 MS patients collected after their diagnosis, plus samples taken five or more years earlier when they joined the military. The researchers also looked at comparable blood samples from 250 healthy veterans.
Between the large number of subjects and the before-and-after timing of the samples, it was “a phenomenal cohort of individuals to look at to see how this kind of autoimmunity develops over the course of clinical onset of this disease,” said Zamecnik.
A consistent signature of MS
Using a mere one-thousandth of a milliliter 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% 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% of all people, yet has been flagged in previous studies as a contributing cause for MS.
Years before diagnosis, this subset of MS patients had other signs of an immune war in the brain. Ahmed Abdelhak, MD, co-author of the paper and a postdoctoral researcher in the UCSF laboratory of Ari Green, MD, found that patients with these autoantibodies had elevated levels of neurofilament light (Nfl), a protein that gets released as neurons break down.
Perhaps, the researchers speculated, the immune system was mistaking friendly human proteins for some viral foe, leading to a lifetime of MS.
“When we analyze healthy people using our technology, everybody looks unique, with their own fingerprint of immunological experience, like a snowflake,” DeRisi said. “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
To confirm their findings, the team analyzed blood samples from patients in the UCSF ORIGINS study. These patients all had neurological symptoms and many, but not all, went on to be diagnosed with MS.
Once again, 10% of the patients in the ORIGINS study who were diagnosed with MS had the same autoantibody pattern. The pattern was 100% predictive of an MS diagnosis. Across both the Department of Defense group and the ORIGINS group, every patient with this autoantibody pattern had MS.
“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.”
Many questions remain about MS, ranging from what’s instigating the immune response in some MS patients to how the disease develops in the other 90% of patients. But the researchers believe they now have a definitive sign that MS is brewing.
“Imagine if we could diagnose MS before some patients reach the clinic,” said Stephen Hauser, MD, director of the UCSF Weill Institute for Neurosciences and a senior author of the paper. “It enhances our chances of moving from suppression to cure.”
For funding and disclosures, see the paper.
Other UCSF authors are Ahmed Abdelhak, Ravi Dandekar, Rebecca D. Bair, Kristen J. Wade, Christopher M. Bartley, Asritha Tubati, Refujia Gomez, Camille Fouassier, Chloe Gerungan, Jessica Alexander, Anne E. Wapniarski, Rita P. Loudermilk, Erica L. Eggers, Kelsey C. Zorn, Kirtana Ananth, Nora Jabassini, Sabrina A. Mann, Nicholas R. Ragan, Adam Santaniello, Roland G. Henry, Sergio E. Baranzini, Scott S. Zamvil, Riley M. Bove, Chu-Yueh Guo, Jeffrey M. Gelfand, Richard Cuneo, H.-Christian von Büdingen, Jorge R. Oksenberg, Bruce AC Cree, Jill A. Hollenbach, and Ari J. Green. For all authors, see the paper.

News
The Role of Nanotechnology in Space Exploration
Nanotechnology, which involves working with materials at the atomic or molecular level, is becoming increasingly important in space exploration. By improving strength, thermal stability, electrical conductivity, and radiation resistance, nanotechnology is helping create lighter, more [...]
New Study Challenges Beliefs About CBD in Pregnancy, Reveals Unexpected Risks
CBD is gaining popularity as a remedy for pregnancy symptoms like nausea and anxiety, but new research suggests it may not be as safe as many believe. A study from McMaster University found that [...]
Does COVID increase the risk of Alzheimer’s disease?
Scientists discover that even mild COVID-19 can alter brain proteins linked to Alzheimer’s disease, potentially increasing dementia risk—raising urgent public health concerns. A recent study published in the journal Nature Medicine investigated whether both mild and [...]
New MRI Study Reveals How Cannabis Alters Brain Activity and Weakens Memory
A massive new study sheds light on how cannabis affects the brain, particularly during cognitive tasks. Researchers analyzed over 1,000 young adults and found that both heavy lifetime use and recent cannabis consumption significantly reduced brain [...]
How to Assess Nanotoxicity: Key Methods and Protocols
With their high surface area and enhanced physicochemical properties, nanomaterials play a critical role in drug delivery, consumer products, and environmental technologies. However, their nanoscale dimensions enable interactions with cellular components in complex and [...]
Nanotech drug delivery shows lasting benefits, reducing need for repeat surgeries
A nanotechnology-based drug delivery system developed at UVA Health to save patients from repeated surgeries has proved to have unexpectedly long-lasting benefits in lab tests – a promising sign for its potential to help human patients. [...]
Scientists Just Found DNA’s Building Blocks in Asteroid Bennu – Could This Explain Life’s Origins?
Japanese scientists detected all five nucleobases — building blocks of DNA and RNA — in samples returned from asteroid Bennu by NASA’s OSIRIS-REx mission. NASA’s OSIRIS-REx mission brought back 121.6 grams of asteroid Bennu, unveiling nitrogen-rich organic matter, including DNA’s essential [...]
AI-Designed Proteins – Unlike Any Found in Nature – Revolutionize Snakebite Treatment
Scientists have pioneered a groundbreaking method to combat snake venom using newly designed proteins, offering hope for more effective, accessible, and affordable antivenom solutions. By utilizing advanced computational techniques and deep learning, this innovative [...]
New nanosystem offers hope for improved diagnosis and treatment of tongue cancer
A pioneering study has unveiled the Au-HN-1 nanosystem, a cutting-edge approach that promises to transform the diagnosis and treatment of tongue squamous cell carcinoma (TSCC). By harnessing gold nanoparticles coupled with the HN-1 peptide, [...]
Global Trust in Science Is Stronger Than Expected – What’s Next?
A landmark global survey conducted across 68 countries has found that public trust in scientists remains robust, with significant support for their active involvement in societal and political matters. The study highlights the public’s [...]
Microplastics in the bloodstream may pose hidden risks to brain health
In a recent study published in the journal Science Advances, researchers investigated the impact of microplastics on blood flow and neurobehavioral functions in mice. Using advanced imaging techniques, they observed that microplastics obstruct cerebral blood [...]
AI Surveillance: New Study Exposes Hidden Risks to Your Privacy
A new mathematical model enhances the evaluation of AI identification risks, offering a scalable solution to balance technological benefits with privacy protection. AI tools are increasingly used to track and monitor people both online [...]
Permafrost Thaw: Unleashing Ancient Pathogens and Greenhouse Gases
Permafrost is a fascinating yet alarming natural phenomenon. It refers to ground that remains frozen for at least two consecutive years. Mostly found in polar regions like Siberia, Alaska, and Canada, permafrost plays a [...]
Frequent social media use tied to higher levels of irritability
A survey led by researchers from the Center for Quantitative Health at Massachusetts General Hospital and Harvard Medical School has analyzed the association between self-reported social media use and irritability among US adults. Frequent [...]
Australian oysters’ blood could hold key to fighting drug-resistant superbugs
Protein found in Sydney rock oysters’ haemolymph can kill bacteria and boost some antibiotics’ effectiveness, scientists discover An antimicrobial protein found in the blood of an Australian oyster could help in the fight against [...]
First U.S. H5N1 Death Sparks Urgency: Scientists Warn Bird Flu Is Mutating Faster Than Expected
A human strain of H5N1 bird flu isolated in Texas shows mutations enabling better replication in human cells and causing more severe disease in mice compared to a bovine strain. While the virus isn’t [...]