Levels of Certain Inflammatory Proteins May Predict Risk of Relapse

Levels of certain inflammatory proteins in the cerebrospinal fluid, the liquid around the brain and spinal cord, may help predict the risk of relapse activity for individuals with early multiple sclerosis (MS), a new study found.

High levels of three such proteins were predictive of a greater risk of a second relapse in people with early MS, according to researchers, who noted that the proteins “might be of value as prognostic biomarkers in early phases of multiple sclerosis.”

The study, “IL-2, IL-6 and chitinase 3-like 2 might predict early relapse activity in multiple sclerosis,” was published in PLOS One.

Most MS patients experience relapses — times when old symptoms suddenly return or worsen, or when new symptoms suddenly appear. Finding ways to predict the risk of future relapses may help to personalize care, and potentially slow the timeline of the disease’s progression. For example, healthcare providers could possibly give more aggressive treatment to higher-risk patients.

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To learn more, a team of researchers in the Czech Republic conducted analyses of the levels of several inflammatory or nerve-related proteins in the blood and cerebrospinal fluid (CSF) of people with early MS. The 58 patients involved in the study were starting on a disease-modifying MS treatment for the first time. The samples were collected before treatment was started.

Among the participants, 54 had relapsing-remitting MS, and the other four were diagnosed with clinically isolated syndrome (CIS). CIS is the first episode of neurological symptoms that last at least 24 hours and are suggestive of MS.

All were started on either glatiramer acetate (sold as Copaxone, among others) or an interferon therapy. The average time to diagnosis was 1.1 months, and the average time to starting treatment was 3.7 months.

The patients were followed for two years. The scientists then conducted a battery of statistical analyses looking for associations between various biomarkers at the treatment’s start, and outcomes during the follow-up.

The team examined both interleukin-2 (IL-2) and interleukin-6 (IL-6), both inflammatory signaling molecules associated with the activity of a type of immune cell called T-cells. These immune cells are known to participate in the attack that drives MS.

Results showed that increased levels of the IL-2 protein in the CSF — specifically 1.23 pg/mL or higher — were significantly predictive of a shorter time between relapses. A ratio of CSF IL-2 to IL-6 lower than 0.48 also was associated with early relapse activity.

“To the best of our knowledge, no studies have been conducted on CSF IL-2 as a potential predictor of disease course in early MS,” the researchers noted.

Another protein called Chitinase 3-like 1 (CHI3L2) also was predictive of a greater risk of a second relapse when levels in the CSF were 7,900 pg/mL or higher. CHI3L2 is a marker of inflammatory activity by glial cells, a type of nervous system cell that normally helps to support the function of nerve cells that send electrical signals.

Younger age and more severe disability at the start of treatment also were predictive of a shorter time to a second relapse. Specifically, patients younger than age 22 or with a score of 1.5 or higher on the Expanded Disability Status Scale, a measure of disability in MS, were at higher risk of having a second relapse sooner.

Notably, a model that included all these parameters showed that the greater the number of positive biomarkers patients had, the more likely they were to experience a second relapse.

“Assessment of some of the studied biomarkers at the time of diagnostic lumbar puncture might be useful to estimate early relapse activity in MS. The most promising predictors of a worse outcome seem to be CSF IL-2, IL2:IL6 ratio (both in CSF) and CSF CHI3L2,” the researchers concluded.

The team noted that this study is limited by its small size, relatively short follow-up time, and incomplete MRI data. They stressed that further research is needed to validate the results.