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Immunophenotypic signature revealed by cytometry by time of flight (CyTOF) in patients treated with dimethyl fumarate
Author(s): ,
B. Ajami
Affiliations:
Stanford University, Stanford, CA, United States
,
A. Manning Carlson
Affiliations:
Stanford University, Stanford, CA, United States
,
P. Ho
Affiliations:
Stanford University, Stanford, CA, United States
,
G. Nolan
Affiliations:
Stanford University, Stanford, CA, United States
L. Steinman
Affiliations:
Stanford University, Stanford, CA, United States
ECTRIMS Online Library. Manning Carlson A.
Oct 12, 2018; 229024
Aaron Manning Carlson
Aaron Manning Carlson
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Abstract: P1184

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Biomarkers

Dimethyl fumarate (DMF) is a disease-modifying therapy used in the treatment of RRMS. It was proven in two large, clinical trials to be effective in prevention of clinical relapses. However, the mechanism of action remains unclear and cellular biomarkers of treatment response are lacking. Cytometry by Time-of-Flight (CyTOF) allows for high-dimensional proteomic profiling of single-cells, with simultaneous analysis upward of 40 markers. In this 12-month longitudinal study we use CyTOF to describe a possible immune signature of peripheral blood mononuclear cells (PBMCs). Such a signature might reveal the cell populations that are uniquely associated with DMF treatment and may serve as a biomarker for outcome. Patients were enrolled in this study from June 2014 to August 2015. Patients met criteria if they had a diagnosis of multiple sclerosis, were aged 18-65 years old, and were naïve to DMF. Patients were excluded if they had prior exposure to disease modifying therapy with the exception of glatiramer acetate and beta-interferon. Clinical exams and EDSS were completed at enrollment, 6 months, and 12 months. Blood draws were completed at enrollment, 3 months, 6 months, and 12 months. CyTOF panel was designed based on known cellular surface markers and immune activation pathways. Changes in unique subpopulations of CD8+ T cells, CD4+ T cells, memory B cells and granulocytes were identified by CyTOF in response to DMF treatment in all patients. Subpopulations associated with inflammatory responses decreased, while subpopulations associated with mitigation of the inflammatory responses increased, supportive of the anti-inflammatory effect of DMF. This study identifies a distinct cellular signature in PBMCs of dimethyl fumarate treatment. Our findings are supportive of a recently discovered putative molecular mechanism of action of inhibition of protein kinase C theta (PKCθ) by DMF. Further studies are needed to confirm this as a durable biomarker of treatment response.
Disclosure: Bahareh Ajami: Nothing to disclose.
Aaron Manning Carlson: Nothing to disclose.
Peggy Ho: Nothing to disclose
Garry Nolan:Nothing to disclose
Larry Steinman:Nothing to disclose

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