Abstract Details

Title Treg Cell Function and Related Cytokines and Chemokines Changes during Alemtuzumab Treatment: A 24 Months Immunological Study

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 148

Objective

Background BACKGROUND: Alemtuzumab is associated with a long-standing reduction of T CD4+ subset.

Design/Methods DESIGN/METHODS: Multicenter follow-up of alemtuzumab-treated relapsing-remitting multiple sclerosis(RRMS)patients in CAMMS323 or 324 trials.FACS analysis of Treg, Th1 and Th17 cells. Immunological molecule mRNA levels (chemokines:CCL-11,CXCL-10;chemokine receptors:CCR-4,CCR-6; cytokines:IFN?,TGF?,TNF?,IL-1?,IL-2,IL-6,IL-10,IL-12p35,IL-17A,IL-17F,IL22,IL-23,IL-26,IL-27;and T-bet,ROR?t,Foxp3) quantified by TaqMan® low density array (TLDA) real-time polymerase chain reaction in whole blood.Treg suppressor activity assessed at M12 and M24 by ELISPOT on PBMC depleted of CD25highT cells and activated with myelin basic protein (MBP) or anti-CD3-CD28. Timepoints:Baseline(before first alemtuzumab course);Month (M)6,M12,M18,M24:6,12,18,24 months after first course.M12 was before second Alemtuzumab course. The relative mean difference between baseline and subsequent timepoints estimated through the formula:(Timepoint-Baseline)/Baseline, and significance of the differences tested.

Results RESULTS: Twenty-nine patients from 6 European sites.After alemtuzumab, CD4+ lymphocytes decreased from 45 to 14%.Th17 increased at M18; no significant variation were observed in Th1 cells. T-bet and IL-23 decreased; Foxp3, TGF?, IL-10 and IL-27 increased from M6 to M24. Treg cell specific suppressive function on MBP auto-reactive Th1 and Th17 cell increased only at M24, whereas the number of Treg cells and their overall suppressor function did not significantly change during the follow-up. Four Relapses were observed in 3 patients. No occurrence of severe autoimmune disease or changes of thyroid function.

Conclusions CONCLUSIONS: The overall alemtuzumab-induced CD4+ lymphocyte depletion might relate to the reduction of MS disease activity.The increase of suppressor cytokines IL-27,IL-10,TGF? and of MBP-specific Treg suppressor function could have resulted in the decrease of T-bet, modulating the anti-CNS pathogenicity of Th1 and Th17 cells. The lack of an increase of the overall Treg suppressor function might allow the development in some patient of non MBP-specific autoimmunity.The further long-term follow-up could provide information on the timing of subsequent courses of Alemtuzumab in individual patients.

Authors/Disclosures
PRESENTER	No disclosure on file
Marinella Clerico, MD (University of Torino)	Dr. Clerico has nothing to disclose.
	No disclosure on file
Cameron Brennan	Cameron Brennan has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Anton Vladic, MD (Spektar Putovanja)	No disclosure on file
Mario Habek, MD (University of Zagreb, School of Medicine)	Dr. Habek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Habek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck . Dr. Habek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Habek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca. Dr. Habek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Habek has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Habek has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Habek has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Habek has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Ivan Adamec (University Hospital Center Zagreb)	Ivan Adamec has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Ivan Adamec has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Ivan Adamec has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Ivan Adamec has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Ivan Adamec has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Ivan Adamec has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Ivan Adamec has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sandoz. Ivan Adamec has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zentiva. Ivan Adamec has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Jadran Galenski laboratorij. Ivan Adamec has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Phoenix farmacija.
Vesna V. Brinar, MD, PhD (Outpatient Clinic Cortex, Neurology)	No disclosure on file
Eleonora Cocco	No disclosure on file
Jessica Frau	No disclosure on file
Pietro Annovazzi	No disclosure on file
	No disclosure on file
Ivana Kovarova (Teva Pharmaceuticals, s.r.o.)	No disclosure on file
Luca Durelli, MD (Divisione Universitaria di Neurologia)	No disclosure on file

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