Abstract Details

Title Profiling of Peripheral Blood Lymphocytes in Multiple Sclerosis Patients Discontinuing FTY720 Therapy

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 195

Objective

Background BACKGROUND: The therapeutic effect of FTY720 has been linked to removal of CCR7 expressing lymphocytes (naive and central memory CD4 and CD8 T cells) from the peripheral circulation. Previously, (Galleguillos, ECTRIMS 2012) we found that mean lymphocyte counts of patients on long-term (5-8 years) FTY720 therapy ranged between 0.2-0.6 x109 cells/L; fluctuations in counts correlated with the proportion of CD8+CCR7- cells, while the proportion of CCR7+ cells did not.

Design/Methods DESIGN/METHODS: Peripheral blood lymphocytes were obtained and analyzed at multiple times points (days 1,3,7,9) in patients discontinuing FTY720 treatment for up to 14 days as allowed by clinical guidelines. Multi-parameter flow cytometry was used to assess lymphocyte subsets (CD4, CD8, and CCR7) on whole blood samples; results were correlated with total lymphocyte counts (TLCs).

Results RESULTS: Subset analyses on samples with TLCs <0.6 (n=4, mean 3 days off-treatment) showed no significant increase in proportion of CCR7+CD4+ (12.5±2.5%) or CD8+ T cells (6.6±1.2%) compared to our previous studied cohort (n=31) when patients were receiving treatment (11.0±1.3 % and 3.2±0.4% respectively). The CD4:CD8 ratio (1:3) was increased compared to the treated cohort (1:5). For samples with TLCs >0.6 but <1.0 (n=5, mean 7 days off-treatment), the mean proportion of CCR7+CD4+ (37.4±8.4%) and CD8 (16.4±3.2) cells was significantly increased compared to the treated cohort. The CD4:CD8 ratio was significantly increased (1:1.25) compared to the <0.6 TLC samples.

Conclusions CONCLUSIONS: Our results indicate that at TLC values >0.6, lymphocyte subsets sequestered by current FTY720 therapy dosage began to egress into the periphery. To be determined is whether these emerging T cells contain disease-relevant subsets, and whether such immune cell profiles can predict those that are found in patients with similar TLCs resulting from lower FTY720 doses.

Authors/Disclosures
David Henault PRESENTER	No disclosure on file
Lorna Galleguillos	No disclosure on file
Craig S. Moore, PhD (Memorial University of Newfoundland)	Dr. Moore has nothing to disclose.
Yves L. Lapierre, MD	No disclosure on file
Amit Bar-Or, MD, FRCPC (University of Pennsylvania)	Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or 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. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.
Jack P. Antel, MD, FAAN (Montreal Neurologic Hospital)	Dr. Antel has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for sanofi, roche, biogen, wave,nervgen. The institution of Dr. Antel has received research support from Novartis canada bristol myers squib. Dr. Antel has a non-compensated relationship as a past president with ACTRIMS that is relevant to AAN interests or activities.
Stephen M. Newman, MD	Dr. Newman has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Biogen. Dr. Newman 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. Newman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme . Dr. Newman has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen.

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