Early identification of interferon-beta responders by ex vivo testing in patients with multiple sclerosis

Abstract

Interferon-beta (IFN-β) is an effective treatment for a subgroup of patients with multiple sclerosis (MS). The mechanism of action as well as the pathophysiological basis of responsiveness to IFN-β is not well understood. To improve treatment considerations in MS patients predictive markers for response to IFN-β therapy at early timepoints are needed. Here we correlated changes in serum cytokine levels (IL-13, IL-10, IL-5, IL-4, IFN-γ) with the clinical response to IFN-β treatment. Serum cytokine levels of 77 untreated and 43 IFN-β treated relapsing–remitting MS patients (RRMS) were measured by ELISA, including longitudinal measurements in 17 patients. We found a significant upregulation of IL-10 and IL-5 serum cytokine levels during IFN-β therapy. However, clinical response was only associated with IL-10 serum levels ( p = 0.038; positive predictive value 0.95, negative predictive value 0.43) but not with IL-5. The predictive power was increased by a combined testing of IL-10 with expression of co-signaling molecules on monocytes, that were previously shown to change during IFN-β therapy. In a subgroup of 17 patients testing of 4 markers had a positive and negative predictive value of 1.0 for at least 2 of these markers being positive in treatment responders. The results suggest that serum IL-10 is useful to predict treatment response to IFN-β particularly in combination with a panel of other IFN-β dependent parameters.