Blood-Based Immune Signatures Identified to Personalize MS Treatment

It has never been quite clear whether certain features of MS are associated with distinct immune signatures or would benefit from any particular therapies.

A new study out of Germany, published in Science Translational Medicine in June 2024, looked at peripheral blood mononuclear cells and serum collected from two independent cohorts of patients with MS to identify three endophenotypes of the disease.

Heinz Wiendl, director of the department of neurology with the institute for translational neurology at the University of Münster, served as senior author for the paper, and noted the data analyzed proved that peripheral blood analysis can be used to guide personalized treatment regimens for patients with MS.

These peripheral blood immune signatures distinguished patients with distinct clinical disease trajectories and efficacy of interferon-β treatment. These data suggest that peripheral blood analysis could be used to guide personalized treatment regimens for patients with MS.

The cohorts were comprised of 541 patients with early MS—309 as part of the discovery cohort and 232 as part of the validation subset. By looking at the data, the researchers identified a trio of distinct peripheral blood immunological endophenotypes by a combination of high-dimensional flow cytometry and serum proteomics, followed by unsupervised clustering.

What’s more, by looking at longitudinal clinical and paraclinical follow-up data in both cohorts, Wiendl and his team discovered these endophenotypes were associated with disease trajectories of inflammation versus early structural damage.

“Investigating the capacity of immunotherapies to normalize endophenotype-specific immune signatures revealed discrete effect sizes as illustrated by the limited effect of interferon-β on endophenotype 3–related immune signatures,” he said in the paper. “Accordingly, patients who fell into endophenotype 3 subsequently treated with interferon-β exhibited higher disease progression and MRI activity over a 4-year follow-up compared with treatment with other therapies.”

This led Wiendl and his team to thoerize that ascertaining a patient’s blood immune signature before immunomodulatory treatment initiation could facilitate prediction of clinical disease trajectories. Additionally, this would also enable personalized treatment decisions based on pathobiological principles.

The hope is that data from the study can be used by researchers in the future to test and confirm how different MS treatments work for patients with these immune signatures, and/or to find other potential therapies that would be beneficial.

To help in this regard, Wiendl plans to develop a test to help researchers better discriminate between the E subgroups, and he’s also created an app using the data that was discovered in the study.