Researchers uncover an immune signature in some people with MS long before their first symptom

Further research may offer clues to what triggered their MS and will lay the groundwork for detecting and treating MS much earlier to reduce future worsening

Investigators at the University of California, San Francisco and collaborators leveraged a massive collection of blood samples to search for an immune antibody signature that could identify people in the pre-clinical stage of MS. They discovered a unique pattern of immune antibodies in about 10% of people who went on to develop MS 5 years later. This study, partially funded by a targeted research program of the National Multiple Sclerosis Society, begins to lay the groundwork for identifying people at high risk for developing MS. This and other studies are getting us closer to identifying people with MS prior to the onset of disease-specific symptoms. Treating people in this pre-clinical stage of MS would likely lead to the delay or perhaps even prevention of clinical disease.

Background and Details: Accumulating evidence suggests that MS may begin years before a person experiences a first recognizable symptom of the disease. Research also shows that getting and staying on an MS disease-modifying therapy is the best way to reduce relapses, delay progression of disability, and limit new disease activity. To further research on how to identify MS before it causes nervous system damage, the National MS Society funded targeted research on early detection of MS. This study is just one of several studies conducted from that targeted funding.

• A collaborative team led by Michael Wilson, MD, took advantage of blood (serum) samples collected by the Department of Defense from millions of active-duty military personnel. A portion of those individuals eventually developed MS years later.
• There is evidence that viruses may play a role in the development of MS in people whose genes and other factors put them at risk. Antibodies are proteins that our immune system makes to target foreign agents like viruses, but they can also sometimes inappropriately attack our own body's self proteins.
• Using advanced tools, Dr. Wilson and colleagues probed the serum samples for antibodies that formed patterns, comparing antibodies of people who eventually developed MS to those of people who did not. About 10% of individuals who developed MS years later had a unique antibody profile that consistently predicted that they would develop MS.
• They also found that samples from people who ultimately developed MS had higher than normal levels of a protein fragment (neurofilament light) that is an emerging biomarker or indicator of nerve damage and inflammation, confirming that the antibody profile was relevant to MS.

Why does this matter? This study contributes to the goal of developing ways to detect MS before it causes too much damage. This would enable early intervention to stop the progression to full-blown MS.

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"An autoantibody signature predictive for multiple sclerosis, " by Colin R. Zamecnik, Gavin M. Sowa, Ahmed Abdelhak, Ravi Dandekar, Rebecca D. Bair, Kristen J. Wade, Christopher M. Bartley, Kerry Kizer, Danillo G. Augusto, Asritha Tubati, Refujia Gomez, Camille Fouassier, Chloe Gerungan, Colette M. Caspar, 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, Joseph J. Sabatino Jr., Riley M. Bove, Chu-Yueh Guo, Jeffrey M. Gelfand, Richard Cuneo, H.-Christian von Büdingen, Jorge R. Oksenberg, Bruce A. C. Cree, Jill A. Hollenbach, Ari J. Green, Stephen L. Hauser, Mitchell T. Wallin, Joseph L. DeRisi & Michael R. Wilson, was published online on April 19, 2024 in Nature Medicine.