Immune signatures may predict MS course, treatment response

Researchers have identified three distinct immune signatures in the blood of people with early multiple sclerosis (MS) that seem to be linked to specific disease trajectories and response to treatment, potentially offering a path to personalized care.

“These findings represent a pivotal shift towards precision medicine in MS,” Heinz Wiendl, MD said in a press release. “By understanding the individual immune system variations among patients, we can move closer to personalized treatment plans that are more effective and have fewer side effects.” Wiendl, who heads the Department of Neurology with Institute of Translational Neurology at the University of Münster in Germany, co-led the study, “Multiple sclerosis endophenotypes identified by high-dimensional blood signatures are associated with distinct disease trajectories,” which was published in Science Translational Medicine.

MS is an autoimmune disease where the immune system attacks the protective covering of nerve fibers in the brain and spinal cord, causing a range of symptoms. Which ones manifest and how they change as the disease progresses varies widely from patient to patient.

While many treatment options are available, the selection of one is made based on certain parameters of disease activity and severity, and ignores variations in the underlying immune responses that drive the condition. This is mostly because there’s still a gap in understanding how specific immune signatures may predict the course of disease or which patients are most likely to respond to specific medications.

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Assessing MS immune signatures

“Ascertaining a patient’s blood immune signature before immunomodulatory treatment initiation may facilitate prediction of clinical disease trajectories and enable personalized treatment decisions,” wrote researchers at the University of Münster, who collaborated with the German Competence Network Multiple Sclerosis to analyze data from 309 patients with early MS whose symptoms started less than two years before and who hadn’t received any previous treatment.

The researchers assessed each participant’s immune signatures in detail by counting the number of multiple types of circulating immune cells. Then, using machine learning and algorithms to cluster data sets and discover hidden patterns, they identified three different endophenotypes, that is, MS subgroups, defined by distinct immune signatures.

These signatures remained stable in individual patients for up to nine years, indicating they are intrinsic to each person’s disease. They were also confirmed in an independent group of 232 patients with early MS.

“Our data demonstrate that early MS consists of different immunological endophenotypes characterized by distinct cellular signatures, potentially reflecting differential immunological pathways involved in disease pathogenesis,” wrote the researchers, who then looked at whether the three immune signatures were associated with distinct disease trajectories.

Patients with one signature had higher inflammatory disease activity with multiple relapses in the first year, more frequent use of high-efficacy medications, higher number of inflammatory brain lesions, and a rapid accumulation of disability. Another group had markers that indicated greater structural damage in the brain and disease severity, with increased disability at the start of the study, impaired cognition, and higher levels of nerve damage biomarkers.

This led the researchers to name the groups “inflammatory” and “degenerative.” The third needs more details to be fully characterized.

Along with distinct disease courses, patients in each group differed in how they responded to certain MS treatments. For example, interferon-based medications didn’t work well for those in the inflammatory endophenotype, who progressed more rapidly and showed greater MRI activity over up to four years of follow-up than patients with the same signature treated with glatiramer acetate, which is sold as Copaxone, among others, and Tecfidera (dimethyl fumarate).

“Our study not only challenges the current treatment paradigm, but also helps to provide a practical tool for clinicians to predict disease progression and treatment response,” said Luisa Klotz, MD, who co-led the study from the University of Münster.

Checking a patient’s blood for a specific immune signature before starting treatment could help personalize care and improve clinical outcomes. “This could significantly improve the quality of life for individuals living with MS,” Klotz said.