Contributions
Abstract: EP1487
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 15 Immunology
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.
Objective: To evaluate an extensive panel of leukocyte subpopulations in peripheral blood as potencial biomarkers of therapeutic response to fingolimod.
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 < 0.001) and transitional B- cells (baseline: 10.5 ± 12.3 % vs month +1: 18.7 ± 14.6 %, p < 0.001) was observed. Interestingly, lymphocyte subpopulations were significantly different in responder patients already at baseline, highlighting a lower percentage of Recent Thymic Emigrants (responder: 4.0 ± 1.4 % vs non-responder: 7.4 ± 1.9 %,
p < 0.000).
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 < 0.05) as well as Th1Th17 (Th1Th17 TCM: relapsed: 15.4 ±6.2% vs non-relapsed; 10.5 ± 4.1%, p < 0.05) at baseline compared to relapse-free patients.
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: Nothing to disclose
Abstract: EP1487
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 15 Immunology
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.
Objective: To evaluate an extensive panel of leukocyte subpopulations in peripheral blood as potencial biomarkers of therapeutic response to fingolimod.
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 < 0.001) and transitional B- cells (baseline: 10.5 ± 12.3 % vs month +1: 18.7 ± 14.6 %, p < 0.001) was observed. Interestingly, lymphocyte subpopulations were significantly different in responder patients already at baseline, highlighting a lower percentage of Recent Thymic Emigrants (responder: 4.0 ± 1.4 % vs non-responder: 7.4 ± 1.9 %,
p < 0.000).
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 < 0.05) as well as Th1Th17 (Th1Th17 TCM: relapsed: 15.4 ±6.2% vs non-relapsed; 10.5 ± 4.1%, p < 0.05) at baseline compared to relapse-free patients.
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: Nothing to disclose