New biomarker may help identify MS patients for BTK inhibitors

Balance between 2 molecules seen as inflammation marker

Written by Marisa Wexler, MS | January 7, 2026

• A molecule ratio may identify MS patients with brain inflammation.
• This biomarker could help select patients for BTK inhibitor treatment.
• BTK inhibitors reduce inflammation and nerve damage in MS models.

The balance between two immune signaling molecules — CXCL13 and BAFF — may help identify the hard-to-treat inflammation in the brain and spinal cord that’s thought to be a major driver of disability progression in multiple sclerosis (MS), a study found.

The findings may help identify which patients are most likely to benefit from BTK inhibitors — treatments that are believed to target this form of compartmentalized inflammation — and aid in selecting candidates for future clinical trials.

BTK inhibitors have yielded mixed results in clinical trials.

“We think we have uncovered a potential biomarker that signals a patient is experiencing so-called ‘compartmentalized inflammation’ in the central nervous system, a phenomenon which is strongly [linked] to MS progression,” Jen Gommerman, co-author of the study and chair of immunology at the University of Toronto, said in a university news story.

The study, “Lymphotoxin-dependent elevated meningeal CXCL13:BAFF ratios drive gray matter injury,” was published in Nature Immunology.

Inflammation drives progressive MS

Unlike the inflammation seen in relapsing forms of MS, where immune cells repeatedly enter the brain and spinal cord to cause damage, progressive forms of the disease are primarily driven by inflammation within the central nervous system.

Immune cells settle in the membranes surrounding the brain and spinal cord, where they form clumps called tertiary lymphoid tissues (TLTs), and continue driving damage in the cortex, the outer layer of the brain, even when peripheral inflammation is well controlled.

TLTs resemble lymph nodes and are composed largely of B-cells, immune cells that produce antibodies and play a prominent role in driving MS. However, exactly how they form and how best to target them has remained unclear.

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