T cell cytokine signatures: Biomarkers in pediatric multiple sclerosis

Although multiple sclerosis is predominantly regarded as a disease of young adulthood, up to 5% of MS patients are diagnosed prior to age eighteen. The predominant form of MS is relapsing-remitting characterized by exacerbations of symptoms followed by periods of remission. The majority of disease modifying drugs target T cell proliferation or block migration into the central nervous system. Although these treatments reduce relapses, disease progression still occurs, warranting therapeutic strategies that protect the CNS. Biomarkers to indicate relapses would facilitate a personalized approach for add-on therapies that protect the CNS. A multiplex cytokine bead array was performed to detect T cell associated cytokines in sera from patients 6-20years of age with pediatric onset MS clinically diagnosed in relapse or remission compared to healthy control patients. Of the 25 cytokines evaluated, 17 were increased in patients clinically diagnosed in relapse compared to sera from control patients in contrast to only 9 cytokines in the clinically diagnosed remission group. Furthermore, a linear regression analysis of cytokine levels in the remission population showed 12 cytokines to be statistically elevated as a function of disease duration, with no effect observed in the relapse population. To further explore this concept, we used a multivariable stepwise discriminate analysis and found that the following four cytokines (IL-10, IL-21, IL-23, and IL-27) are not only a significant predictor for MS, but have important predictive value in determining a relapse. Since IL-10 and IL-27 are considered anti-inflammatory and IL-21 and IL-23 are pro-inflammatory, ratios of these cytokines were evaluated using a Duncan's multiple range test. Of the six possible combinations, increased ratios of IL-10:IL-21, IL-10:IL-23, and IL-10:IL-27 were significant suggesting levels of IL-10 to be a driving force in predicting a relapse.