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Abstract Details

Extensive Long-term Immune Cell Profiling Reveals Further Targets of Oral Cladribine in MS
Multiple Sclerosis
MS and CNS Inflammatory Disease Posters (7:00 AM-5:00 PM)
209

We aimed to expand the knowledge about the mode of action for cladribine (CLAD), an immune reconstitution therapy approved for multiple sclerosis (MS), beyond the known effects on immune cell subsets of the adaptive and innate immune system. 

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system (CNS) with presumed autoimmune etiology. The current understanding of the pathogenesis includes the peripheral activation of myelin-reactive effector CD4 T helper (TH) 1 cells, memory B cells and TH17 cells. Furthermore, there is emerging evidence for a key role of TH17.1 cells, which share inflammatory features of TH17 and TH1 cells.

We studied depletion and restitution kinetics as well as cytokine profiles of immune cell subsets in peripheral blood of 18 patients with MS by flow cytometry over a period of 24 months after intake of CLAD. 
We show a selectivity of CLAD towards central memory T cells and memory B cells and detected a hyper-repopulation of maturing B cells. Moreover, counts of classical (-65%) and various non-classical TH17 cells (-84% to -87%) were markedly reduced 24 months after treatment start, and were comparable with depletion rates of class-switchedmemory B cell phenotypes (-87% to -95%). Importantly, reductions in TH cells were greater in the second treatment year. Regulatory lymphocytes and monocytes were spared. Antibody-producing B cells, cytotoxic T cells and natural killer cells (NK) were affected to a lesser extent. Natural killer T cells (NKT) were selectively depleted in year two.

Extensive and prolonged immune cell profiling revealed a depletion of different B cell and TH17 populations as well as more robust or exclusive changes for some subsets after the second course of treatment. Further studies are required to elucidate whether these changes are paramount for the consistent and prolonged disease-modifying effect of CLAD. 
Authors/Disclosures
Tobias Moser
PRESENTER 		Mr. Moser has nothing to disclose.
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.
Johann Sellner, MD, FAAN (Neurologie, LK Mistelbach) Dr. Sellner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Boehringer, Celgene, Immunic, Merck, Novartis, Roche, Sanofi. Dr. Sellner has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion, Biogen, Immunic, Merck, Novartis, Roche, Sanofi. Dr. Sellner has received personal compensation in the range of $0-$499 for serving as a Reviewer with Ethics Committtee.