Abstract Details

Title Immunological Effects by Longterm Fingolimod Therapy in MS

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 158

Objective

Background BACKGROUND: Fingolimod (FTY) is a sphingosine 1-phosphate (S1P) receptor modulator and inhibits lymphocyte egress from secondary lymphoid tissues, resulting in peripheral lymphopenia.

Design/Methods DESIGN/METHODS: In a prospective cohort, 23 MS patients were immunologically analyzed at different timepoints (up to 2 years) regarding peripheral (blood) and CNS (CSF) immune system. Effects on different immune cell subsets were investigated in-vivo using FACS analysis. In addition, soluble factors as S1P were analyzed.

Results RESULTS: In CSF, total cell count was significantly decreased from 6.33MPt/l to 2,47MPt/l after 4 months of FTY treatment. In particular, decrease of CD4 T-cells was more pronounced than CD8 T-cell decrease (ratio CD4/CD8: 4.6 to 0.8). B-cells decreased (0.36MPt/l to 0.15MPt/l) while plasma-cells were not affected. Larger effects were seen in peripheral immune compartment after. Some populations like CD3-CD56+NK-cells and CD10+B-cells as well as monocytes and granulocytes remained stable. Early immunomodulatory effects could be already detected six hours after first FTY administration while main changes of immune cell composition reached a steady state after 2 weeks. Regarding absolutely reduced CD4 cells, a relative increase of CD39+Treg (plus 350%) and decrease of CD154+TH17 (minus 73%) cells could be observed during therapy which was even more pronounced in the longterm (12 months). S1P concentration decreased significantly during therapy in CSF (2.12nmol/l to 0.71nmol/l) as well as in serum (399.73nmol/l to 310.62nmol/l).

Conclusions CONCLUSIONS: FTY has significant effects to the peripheral as central immune system. First treatment effects could be seen first six hours after first drug administration. As additional mechanism of action, we could observe - especially in the longterm - a modulation of Treg/TH17 balance in favor of Treg cells. S1P concentration was decreased by FTY treatment, more pronounced in the CSF than in serum.

Authors/Disclosures
Tony Sehr PRESENTER	No disclosure on file
Undine Hainke (Lenkr of Clinical Neuroscience)	No disclosure on file
	No disclosure on file
	No disclosure on file
Tjalf Ziemssen, MD, FAAN (University Clinic Dresden)	Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS . Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Dresden Internation University. The institution of Dr. Ziemssen has received research support from Novartis. The institution of Dr. Ziemssen has received research support from Merck. The institution of Dr. Ziemssen has received research support from Sanofi. The institution of Dr. Ziemssen has received research support from BMS. The institution of Dr. Ziemssen has received research support from Roche.
Joshua Z. Willey, MD, FAAN (Columbia University)	Dr. Willey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Edwards Scientific. Dr. Willey has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for RECARDIO. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbott. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BrainQ. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of the American College of Cardiology. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Uptodate. The institution of Dr. Willey has received research support from NIH. Dr. Willey has received personal compensation in the range of $500-$4,999 for serving as a Review chapter author, MKSAP 16-20 with American College of Physicians.

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