Association between proteins may predict early MS disease activity

An association between the proteins IgG1 and CXCL10 in the fluid around the brain may help predict the risk of future disease activity for people in the early stages of multiple sclerosis (MS).

That’s according to “CXCL10/IgG1 Axis in Multiple Sclerosis as a Potential Predictive Biomarker of Disease Activity,” which was published in Neurology Neuroimmunology and Neuroinflammation.

A number of studies have examined whether levels of inflammatory molecules in the cerebrospinal fluid (CSF) can help predict the risk of future disease activity in MS, but they’ve focused mostly on the predictive power of individual ones, which fails to capture the complexity of interactions among them. The CSF is the fluid that surrounds the brain and spinal cord.

Here, researchers analyzed CSF samples from 47 people with early MS disease — 23 with relapsing-remitting MS (RRMS) and 24 with clinically isolated syndrome (CIS), which is a first attack of MS-like disease. In all them, CSF was collected as part of diagnostic procedures; patients weren’t being treated when their CSF was collected.

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All were followed for a year after their CSF was collected. In this time, 18 patients — 10 with RRMS and eight with CIS — saw new disease activity. Based on the 2017 McDonald criteria, the set of guidelines that aid in diagnosing clinically definitive MS, the eight CIS patients were reclassified with RRMS after having new disease activity. Those who had disease activity were on average much younger than those who didn’t.

The researchers analyzed levels of 60 proteins in the patients’ CSF, specifically choosing proteins made in the CSF during MS-driving inflammation.

“These proteins’ alterations may have a direct role involved in MS [development], enhancing our understanding of the disease,” they said.

The CSF samples from RRMS and CIS patients were compared with samples from 27 people with noninflammatory neurological disorders like migraine. Sixteen proteins were identified that were significantly elevated among MS patients.

“These 16 proteins play crucial roles in modulating neuroinflammatory processes, underscoring the prominent inflammatory nature of the disease,” said the researchers, who then constructed detailed mathematical models to assess the relationships between the 16 proteins. Then, statistical tests helped look for significant predictors of disease activity.

“We harnessed advanced network strategies to model the relationship between MS disease activity and 16 MS-specific proteins,” the scientists wrote, noting the network approach let them “unveil patient-specific changes, leading to a more precise identification of altered pathways in disease conditions and critical molecules that represent these altered pathways.”

The patients who had disease activity in the year of follow-up tended to have a stronger association between levels of IgG1, a type of antibody, and CXCL10, a signaling molecule that helps govern the activity and movement of immune cells.

Using a cutoff value of 0.3144 to distinguish those with and without such a correlation, the researchers found that patients with a positive correlation took a median of 5 months to see disease activity, while no specific timing was observed among those without a correlation.

The same trend was seen in the overall patient group and in the subset of patients who’d been diagnosed with CIS at the study’s start, suggesting the “IgG1-CXCL10 interaction may play a crucial role in mediating disease activity, particularly in the earlier phase of the disease,” said the researchers, who noted that CXCL10 likely helps drive the production of antibodies like IgG1 in MS, which could explain why this association seems to be predictive of disease activity.

Larger studies are needed to validate their findings, they said.