Predictive biomarkers for optimal therapeutic response to fingolimod treatment in MS patients

Objective: To evaluate an extensive panel of leukocyte subpopulations in peripheral blood as potencial biomarkers of therapeutic response to fingolimod. Background: Fingolimod (FTY720) is one of the first-line therapies for relapsing-remitting multiple sclerosis (RRMS), which sequesters T-cells to lymph nodes through functional antagonism of sphingosine-1-phosphate 1 receptor, thereby reducing the number of potential autoreactive cells migrating to the central nervous system. Design/Methods: Longitudinal analysis of T, B, NK, monocyte and dendritic-cell subpopulations was performed by multiparametric flow-cytometry in 45 RRMS patients at baseline and after +1, +3, +6 and +12 months of fingolimod treatment. Data were analyzed using Kolmogorov-Smirnov test. In case of no-normal distribution, Wilcoxon, U-Mann Whitney or Kruskal-Wallis test were used, as appropriate. Results: Fingolimod treatment induced a severe lymphopenia affecting mainly T and B cells. However, an relative increase of Tregs (memoryTreg: baseline: 3.8 ± 1.0 % vs month +1: 8.8 ± 4.4 % and activatedTreg: baseline: 1.5 ± 0.7 % vs month +1: 3.7 ± 2.1 %, p Patients that suffered clinical relapses during follow-up had higher percentage of CM CD4+ (relapsed: 36.1 ± 8.8 % vs non-relapsed: 27.2 ± 5.2 %, p Conclusions: These results support that immune-monitoring of minor lymphocyte subpopulations in peripheral blood is a powerful tool for the management of patients under fingolimod treatment that may be extrapolable to other immunotherapies. Disclosure: Dr. Quirant-Sanchez has nothing to disclose. Dr. Teniente-Serra has nothing to disclose. Dr. Hervas-Garcia has nothing to disclose. Dr. Presas-Rodriguez has nothing to disclose. Dr. Mansilla has nothing to disclose. Dr. Navarro has nothing to disclose. Dr. Ramo-Tello has nothing to disclose. Dr. Martinez-Caceres has nothing to disclose.