Blood lymphocyte subsets identify optimal responders to IFN-beta in MS.

Abstract

Response to interferon-beta (IFN-beta) treatment is heterogeneous in multiple sclerosis (MS). We aimed to search for biomarkers predicting no evidence of disease activity (NEDA) status upon IFN-beta treatment in MS. 119 patients with relapsing-remitting MS (RRMS) initiating IFN-beta treatment were included in the study, and followed prospectively for 2years. Neutralizing antibodies (NAb) were explored in serum samples obtained after 6 and 12months of IFN-beta treatment. Soluble cytokines and blood lymphocytes were studied in basal samples by ELISA and flow cytometry, respectively. 9% of patients developed NAb. These antibodies were more frequent in patients receiving IFN-beta 1b than in those treated subcutaneous (p=0.008) or intramuscular (p<0.0001) IFN-beta 1a. No patient showing NAb remained NEDA during follow-up. Basal immunological variables are also associated with patient response. Percentages below 3% of CD19+CD5+cells (AUC 0.74, CI 0.63-0.84; OR 10.68, CI 3.55-32.15, p<0.0001; Likelihood ratio 4.28) or above 2.6% of CD8+perforin+T cells (AUC 0.79, CI 0.63-0.96; OR 6.11, CI 2.0-18.6, p=0.0009; Likelihood ratio 5.47) increased the probability of achieving NEDA status during treatment. Basal blood immune cell subsets contribute to identify MS patients with a high probability of showing an optimal response to IFN-beta.