10.3389/fimmu.2018.01560.s001 Lisa Lohmann Lisa Lohmann Claudia Janoschka Claudia Janoschka Andreas Schulte-Mecklenbeck Andreas Schulte-Mecklenbeck Svenja Klinsing Svenja Klinsing Lucienne Kirstein Lucienne Kirstein Uta Hanning Uta Hanning Timo Wirth Timo Wirth Tilman Schneider-Hohendorf Tilman Schneider-Hohendorf Nicholas Schwab Nicholas Schwab Catharina C. Gross Catharina C. Gross Maria Eveslage Maria Eveslage Sven G. Meuth Sven G. Meuth Heinz Wiendl Heinz Wiendl Luisa Klotz Luisa Klotz data_sheet_1_Immune Cell Profiling During Switching from Natalizumab to Fingolimod Reveals Differential Effects on Systemic Immune-Regulatory Networks and on Trafficking of Non-T Cell Populations into the Cerebrospinal Fluid—Results from the ToFingo Successor Study.doc Frontiers 2018 multiple sclerosis cerebrospinal fluid natalizumab fingolimod viSNE spanning-tree progression analysis of density-normalized events immunoregulatory network 2018-07-09 04:22:24 Dataset https://frontiersin.figshare.com/articles/dataset/data_sheet_1_Immune_Cell_Profiling_During_Switching_from_Natalizumab_to_Fingolimod_Reveals_Differential_Effects_on_Systemic_Immune-Regulatory_Networks_and_on_Trafficking_of_Non-T_Cell_Populations_into_the_Cerebrospinal_Fluid_Results_from_the_ToFingo_Succe/6790982 <p>Leukocyte sequestration is an established therapeutic concept in multiple sclerosis (MS) as represented by the trafficking drugs natalizumab (NAT) and fingolimod (FTY). However, the precise consequences of targeting immune cell trafficking for immunoregulatory network functions are only incompletely understood. In the present study, we performed an in-depth longitudinal characterization of functional and phenotypic immune signatures in peripheral blood (PB) and cerebrospinal fluid (CSF) of 15 MS patients during switching from long-term NAT to FTY treatment after a defined 8-week washout period within a clinical trial (ToFingo successor study; ClinicalTrials.gov: NCT02325440). Unbiased visualization and analysis of high-dimensional single cell flow-cytometry data revealed that switching resulted in a profound alteration of more than 80% of investigated innate and adaptive immune cell subpopulations in the PB, revealing an unexpectedly broad effect of trafficking drugs on peripheral immune signatures. Longitudinal CSF analysis demonstrated that NAT and FTY both reduced T cell subset counts and proportions in the CSF of MS patients with equal potency; NAT however was superior with regard to sequestering non-T cell populations out of the CSF, including B cells, natural killer cells and inflammatory monocytes, suggesting that disease exacerbation in the context of switching might be driven by non-T cell populations. Finally, correlation of our immunological data with signs of disease exacerbation in this small cohort suggested that both (i) CD49d expression levels under NAT at the time of treatment cessation and (ii) swiftness of FTY-mediated effects on immune cell subsets in the PB together may predict stability during switching later on.</p>