Abstract Details

Title Phenotypes of Peripheral Blood Mononuclear Cells and Immunoglobulin Analysis under Treatment with Fingolimod: A Prospective Study

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 152

Objective

Background BACKGROUND: Fingolimod inhibits the sphingosine-1-phosphate-dependent lymphocyte egress from secondary lymphoid tissues causing lymphopenia. So far, specific immunological changes have only been analyzed in small patient cohorts.

Design/Methods DESIGN/METHODS: This prospective, multi-center, single-arm, open-label study included 450 RRMS patients receiving 0.5 mg fingolimod over six months. At predefined time points blood samples were obtained. Leukocyte surface marker expressions were analyzed by FACS (CD3, CD4, CD8, CD16, CD19, CD34, CD45RA, CD56, CCR7), whereas sera samples were analyzed for immunoglobulin levels, the presence of varicella-zoster virus antibodies, and for the presence of various cytokines by ELISA.

Results RESULTS: An early decrease in the relative number of CD45+, CD4+, and CD19+ positive cells was detected, which maintained at low levels during follow-up. In contrast, CD56+ NK cells were found to be increased under treatment with fingolimod. Analyses of T cell subpopulations revealed a decrease in naive (CCR7+/CD45RA+) and central memory (CCR7+/CD45RA-) and an increase of effector memory (CCR7-/CD45RA-) cells. Sera concentrations of IgG, IgA, IgM and IgE levels decreased, whereas VZV-antibody levels remained stable over the 6-months treatment period. For the majority of cytokines tested, no significant alterations were found.

Conclusions CONCLUSIONS: Fingolimod induces profound effects predominantly on CD4+ lymphocytes as well as on immunoglobulin levels for the time of treatment. To which extend these findings can be used as biomarkers predicting clinical efficacy and/or safety signals needs to be evaluated in greater detail.

Authors/Disclosures
Thomas Dehmel (Neurology) PRESENTER	No disclosure on file
Jaime Toro, MD, FAAN (Universidad El Bosque)	Dr. Toro has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Watch Neurology .
	No disclosure on file
Clemens Warnke (Klinik Fuer Neurologie, University of Duesseldorf)	The institution of Clemens Warnke has received research support from Novartis. The institution of Clemens Warnke has received research support from Alexion. The institution of Clemens Warnke has received research support from Sanofi-Genzyme. The institution of Clemens Warnke has received research support from Biogen. The institution of Clemens Warnke has received research support from Roche.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Hans-Peter Hartung, MD, FAAN (Heinrich Heine University Medical Faculty)	Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Hartung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Geneuro. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Neurology.
Maria Diaz Lorente, MD (Novartis Pharma GmbH)	No disclosure on file
	No disclosure on file

��ɫ��

��ɫ��