Biomarker Combo Predicts MS in Patients With Radiologically Isolated Syndrome
Researchers have identified a combination of factors that confers a 58.3% risk of the development of multiple sclerosis (MS) over 5 years in people with radiologically isolated syndrome (pwRIS): high serum neurofilament light chain (NfL) z scores and positive immunoglobulin G oligoclonal bands (OBs).
“This risk increased to 81.6% (95% CI, 60.9-91.4) in pwRIS who were younger and positive for immunoglobulin M OBs,” wrote first author Nicolás Fissolo, PhD, of the Universitat Autònoma de Barcelona, Barcelona, Spain, and coauthors of the study, which was published in JAMA Neurology.
The research team analyzed body fluid biomarkers and other characteristics in 273 pwRIS from 33 MS centers to investigate prognostic factors for MS symptoms. Evaluated samples from the patients were taken close to the time of diagnostic magnetic resonance imaging and RIS diagnosis, reflecting the initial stage of radiologically isolated syndrome.
Among pwRIS in the study, the mean age was 38.6 years, and 75.8% were women. Overall, 37% pwRIS developed clinical symptoms of MS over a median follow-up period of 5 years.
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At the time of radiologically isolated syndrome diagnosis, factors most strongly associated with the development of MS symptoms were the presence of immunoglobulin G OBs (researchers reported a 5.09 hazard ratio [HR]), immunoglobulin M OBs (2.58 HR), and a κ free light chain index of 6.1 or more (2.79 HR), according to the study. Additionally, high cerebrospinal fluid NfL levels (1.31 HR) and high serum NfL z scores (1.42 HR) were associated with increased risk.
On the other hand, factors associated with a reduced risk of MS symptom development included high anti-cytomegalovirus titers (0.59 HR) as well as high ultraviolet radiation exposure in year before (0.52 HR) and after (0.54 HR) diagnosis, the study found.
The findings allowed researchers to solidify a biomarker combination predictive of MS prognosis within the first 5 years: high serum NfL z scores and positive immunoglobulin G OBs. In younger pwRIS, the added presence of immunoglobulin M OBs bumped the likelihood of developing MS even higher.
“These results demonstrate that the identification of pwRIS who are at higher risk of developing clinical symptoms is crucial not only for prognosis,” researchers wrote, “but also for guiding treatment decisions, such as determining which individuals may benefit most from early initiation of disease-modifying therapies or enrollment in clinical trials.”
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