Abstract Details

Title Characterization of the Peripheral Blood Transcriptome in Alemtuzumab-Treated Relapsing-Remitting Multiple Sclerosis Patients From the CARE-MS I and II Studies

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-041

Objective To investigate the gene expression signatures of peripheral blood mononuclear cells (PBMCs) in alemtuzumab-treated RRMS patients from the CARE-MS studies (NCT00530348; NCT00548405).

Background Alemtuzumab, a humanized anti-CD52 monoclonal antibody approved for the treatment of RRMS, has demonstrated superior efficacy versus SC IFNB-1a in phase 2 and 3 clinical trials. Alemtuzumab targets CD52, a cell-surface protein predominantly expressed on T and B cells, resulting in rapid depletion and subsequent repopulation of immune cells. A deeper understanding of the underlying mechanism of action of alemtuzumab will facilitate biomarker discovery for potential risk stratification and treatment effect.

Design/Methods Transcriptome analysis was carried out on PBMCs from alemtuzumab-treated RRMS patients. Patients had received alemtuzumab 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. PBMCs isolated from whole blood were collected at baseline (pre-alemtuzumab) and at Months 12 and 24 post-alemtuzumab initiation, and analyzed by RNA sequencing.

Results Gene co-expression modules were identified that represent gene signatures of distinct immune cell types. From baseline to Months 12 and 24, T-cell (ie, CD4, CD8, and CD3) signature expression decreased, whereas B-cell (ie, CD19, CD20, and CD79A) signature expression increased. From baseline to Month 24, the inflammatory signature expression significantly decreased in PBMCs. Characterization of immune signatures reflect known changes in constituent cell populations during and after alemtuzumab treatment, and reveal a less inflammatory milieu 1 year after the second course of alemtuzumab.

Conclusions These results provide insight into the biological effect of treatment at the transcriptional level of immune cell types in addition to the known effects of alemtuzumab on T and B cells. These insights may aid in further understanding of the mechanism of action of alemtuzumab and help inform future biomarker research.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Srinivas Shankara, PhD (Sanofi)	Dr. Shankara has received personal compensation for serving as an employee of Sanofi.
Alan K. Jacobs, MD, FAAN (Satellos Biosciences)	Dr. Jacobs has received personal compensation for serving as an employee of Immunovant, Inc. Dr. Jacobs has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Galler Consulting.
Jean Godin, MD, MBA (Novartis Pharmaceuticals Canada Inc.)	No disclosure on file
	No disclosure on file
	No disclosure on file

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