Blood test can identify MS in some people years before symptoms start

A unique group of antibodies can be used to predict whether someone will develop multiple sclerosis – they were present in about 10 per cent of people with MS years before they developed symptoms.

A distinct group of antibodies appear in blood samples of some people with multiple sclerosis years before they experience symptoms. The antibodies could help diagnose people with the condition sooner, allowing them to begin treatment earlier.

Multiple sclerosis (MS) is an autoimmune disorder in which the immune system attacks the brain and spinal cord. It can take months or even years to diagnose MS as no specific test for the condition exists. This delays treatment, leading to worse outcomes as the disorder progresses.

In multiple sclerosis, autoantibodies mistakenly attack nerve cells
Kateryna Kon/Science Photo Library

Other autoimmune disorders, like type 1 diabetes, can be diagnosed in part by screening for autoantibodies. While antibodies are produced by the immune system to help identify and attack pathogens, autoantibodies are generated against a person’s own cells. Previously, no autoantibodies had been identified for MS.

Colin Zamecnik at the University of California, San Francisco, and his colleagues analysed blood samples collected from 250 people with MS before and after they developed symptoms. Samples came from the US Department of Defense Serum Repository, which stores blood taken from US military members when they enter active duty or visit affiliated healthcare facilities.

On average, samples were drawn five years before and one year after people first experienced MS symptoms. The researchers compared these to repository samples from an equal number of people without MS, matching for age, sex, race and ethnicity.

They mixed each sample into a solution containing more than 750,000 protein fragments, in hopes of identifying proteins that were targeted by autoantibodies present in the blood. The researchers thought that by comparing targeted proteins in pre- versus post-MS samples, they would find autoantibodies that arose after symptoms began.

“But that’s not what we saw at all,” says Zamecnik. Instead, they found an antibody signature that emerged even before symptoms began. The antibodies targeted 54 proteins and were present in a subset of 30 people, 27 of whom had developed MS. “And that signature is there before and after onset of disease,” says Zamecnik, which suggests it may be one of the earliest indicators of MS.

He and his team validated these findings by analysing spinal fluid collected from a separate group of 126 people with neurological symptoms, 103 of which were later diagnosed with MS. The signature was present in 8 people, all of whom had MS.

“We found that it’s actually pretty specific for patients with MS, even if it only captures around 10 per cent of the population,” says Zamecnik. “And this is still really useful.” For instance, the signature could help diagnose MS earlier in some people, he says.

If additional research in larger samples confirms this finding, Asaff Harel at Northwell Health in New York says it “could help us further classify different types of MS or different causes of the condition”. Additionally, the biomarker may determine people at high risk of developing the disease, he says.


medRxivDOI: 10.1101/2023.05.01.23288943

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