Potential biomarker linked to MS progression identified by researchers

Researchers at the University Health Network and the University of Toronto report in Nature Immunology that a high CXCL13-to-BAFF ratio is associated with leptomeningeal (compartmentalized) inflammation seen in progressive multiple sclerosis, based on a new preclinical model and measures in human samples.

Researchers at the University Health Network and the University of Toronto report a potential biomarker linked to multiple sclerosis (MS) progression. The study was published in Nature Immunology and combined a new preclinical model with measurements from human tissue and cerebrospinal fluid. The preclinical model was designed to reproduce grey matter injury and compartmentalized inflammation in the leptomeninges. The researchers focused on the balance between two immune proteins, CXCL13 and BAFF. Key findings: - The new preclinical model mimics grey matter damage and leptomeningeal compartmentalized inflammation that are seen in progressive MS. - In the model the researchers observed about an 800-fold increase in CXCL13 and notably lower levels of BAFF. - Treating the model with Bruton’s tyrosine kinase (BTK) inhibitor drugs restored CXCL13 and BAFF levels toward those seen in healthy states. - In human samples, a higher CXCL13-to-BAFF ratio in post-mortem brain tissue and in cerebrospinal fluid from a living cohort was associated with greater compartmentalized inflammation. - The study notes that about 10 percent of people with MS are initially diagnosed with progressive MS and that Canada records more than 4,300 new MS diagnoses each year, according to MS Canada. Summary: The team proposes that the CXCL13-to-BAFF ratio could serve as a surrogate marker for leptomeningeal inflammation and help identify patients with the inflammation linked to progression. Researchers are working with pharmaceutical groups to examine whether trial participants who responded to BTK inhibitors had higher ratios, and they plan to study the ratio in people with early MS to assess predictive value. The broader clinical usefulness and impact on trials remain under investigation. Funding for the research came from the Canadian Institutes of Health Research, MS Canada, the National Multiple Sclerosis Society, and the United States Department of Defense.