In a discovery that could hasten treatment for patients with multiple sclerosis, scientists have discovered a harbinger in the blood of some people who later went on to develop the disease. University of California – San Francisco 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.

Linking infections with autoimmune 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.

Autoimmune diseases such as MS are believed to result, in part, from rare immune reactions to common infections. Researchers took a technique in which viruses are engineered to display bits of proteins like flags on their surface – called phage display immunoprecipitation sequencing – 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. 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 authors searched 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, and samples taken five or more years earlier when they joined the military. The researchers also looked at comparable blood samples from 250 healthy veterans.  

A consistent signature of MS  

Using 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 percent 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, which infects more than 85 percent of all people, and has been flagged in previous studies as a contributing factor for MS.  
 
Years before diagnosis, this subset of MS patients had other signs of an immune war in the brain. The researchers found that patients with these autoantibodies had elevated levels of neurofilament light, 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. 

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 percent of the patients in the ORIGINS study who were diagnosed with MS had the same autoantibody pattern. The pattern was 100 percent predictive of an MS diagnosis. Across both the Department of Defense group and the ORIGINS group, every patient with this autoantibody pattern had MS. 

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 percent of patients. But the researchers believe they now have a definitive sign that MS is brewing. 

The findings were published in Nature Medicine.