Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients

Abstract

Objective:To evaluate serum cytokine profiles for their utility to determine the heterogeneous responses to interferon (IFN)–β treatment in patients with multiple sclerosis (MS).Methods:Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome receiving de novo IFN-β treatment were included in this prospective, observational study. Number of relapses and changes in disability were assessed 2 years prior to and 2 years after initiation of treatment. Sera were collected at baseline and after 3 months on therapy. Cytokine levels in sera were assessed by Luminex multiplex assays. Baseline cytokine profiles were grouped by hierarchical clustering analysis. Demographic features, changes in cytokines, and clinical outcome were then assessed in the clustered patient groups.Results:A total of 157 patients were included in the study and clustered into 6 distinct subsets by baseline cytokine profiles. These subsets differed significantly in their clinical and biological response to IFN-β therapy. Two subsets were associated with patients who responded poorly to therapy. Two other subsets, associated with a good response to therapy, showed a significant reduction in relapse rates and no worsening of disability. Each subset also had differential changes in cytokine levels after 3 months of IFN-β treatment.Conclusions:There is heterogeneity in the immunologic pathways of the RRMS population, which correlates with IFN-β response.

Emerging Approaches for Validating and Managing Multiple Sclerosis Relapse

“…Additionally, since treatments affect many of these markers (40), it will be critical to have a baseline reading for each patient, and then a longitudinal assessment following treatment, looking at the profile for both relapsing and remitting conditions to determine which markers have the greatest prognostic value for a particular patient. Furthermore, the concentration of some inflammation-related serum biomarkers varies in a circadian manner, thus taking into account the time of day that samples are collected is vital to make meaningful comparisons (41).…”

Pre-treatment T-cell subsets associate with fingolimod treatment responsiveness in multiple sclerosis

“…For other MS disease-modifying therapies (DMTs), variable treatment responses have been linked to differences in pre-treatment immune abnormalities. For example, heterogeneity in baseline type I interferon (IFN) and Th17 activity may explain variability in IFN-β responsiveness 10,11 .…”

A Journey in Science: The Privilege of Exploring the Brain and the Immune System

“…Investigations over the past 7 years, led by Robert Axtell (a postdoctoral fellow in my lab and then a faculty member at Oklahoma Medical Research Foundation), have stratified the different clinical types of the disease we lump together as relapsing-remitting MS. Axtell and colleagues use a combination of cytokine and chemokine profiles on serum and then advanced bioinformatics. We demonstrated that there is heterogeneity in the levels of a battery of cytokines and chemokines in individuals with relapsing-remitting MS, and the levels provide a signature that correlates with the therapeutic response to IFN-β (109).…”

“…So I recommend keeping spirits high with humor. One of my colleagues who employed perhaps the most charming, intelligent and insightful use of humor has been Robert Axtell (109).…”