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Longitudinal analysis of peripheral blood mononuclear cells in lymphopenic and non-lymphopenic relapsing-remitting multiple sclerosis (RRMS) patients treated with dimethyl fumarate
Author(s): ,
M. Nakhaei-Nejad
Affiliations:
Medicine-Neurology, University of Alberta, Edmonton, AB, Canada
,
D. Barilla
Affiliations:
Medicine-Neurology, University of Alberta, Edmonton, AB, Canada
,
C.-H. Lee
Affiliations:
Medicine-Neurology, University of Alberta, Edmonton, AB, Canada
,
G. Blevins
Affiliations:
Medicine-Neurology, University of Alberta, Edmonton, AB, Canada
F. Giuliani
Affiliations:
Medicine-Neurology, University of Alberta, Edmonton, AB, Canada
ECTRIMS Online Library. Nakhaei-Nejad M. Oct 12, 2018; 229030
Maryam Nakhaei-Nejad
Maryam Nakhaei-Nejad
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Abstract: P1190

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

Relapsing remitting multiple sclerosis (RRMS) is an autoimmune disorder of the central nervous system. Dimethyl Fumarate (DMF) is a disease modifying medication that in some cases may cause lymphopenia. An in-depth characterization of peripheral blood mononuclear cells (PBMC) was done by designing multi-color panels that allowed us to identify up to 50 PBMC subtypes. These subpopulations were monitored over time. Patients had been on treatment for a span of 45 days to 4 years at the time of sample collection, with 15 patients being followed longitudinally. 32% of DMF-treated patients developed mild lymphopenia. We monitored the abundance of T and B lymphocytes, monocytes, dendritic cells and natural killer (NK) cells. Regardless of lymphopenia status, the subpopulation CD56highCD16high NK cells was lower in patients that were on treatment for a longer time (r=-0.34, p=0.015). Among monocytes, the classical subtype (CD14+CD16-) was significantly higher in non-lymphopenic (DMF-N) patients over time (r=0.41, p=0.013) and not in the lymphopenic patients (DMF-L). Although T cells were significantly reduced in DMF-L versus DMF-N patients (p = 1.28X10-5), no significant change was observed over time. DMF-L, but not DMF-N, patients who have been treated for longer times had higher CD4+ (r=0.86, p=1.2X10-5) and lower CD8+ T cells (r=-0.79, p=0.00002), causing an increase in CD4-to-CD8 ratio (r=0.79, p=0.0001). Within CD4+, the naïve subtype (CD45RA+CCR7+) was higher (p=0.003), while the effector memory (CD45RA-CCR7-) was lower (p=0.006) in DMF-L compared to DMF-N. Next, we analysed T helper (Th) cells. Only Th22 had higher levels in DMF-N over time (r=0.43, p=0.022) and no change in lymphopenic patients. Although the overall B cell population did not change over time, regardless of lymphopenia status, the CD27+IgD- B cells were lower in patients that were treated for longer times (r=-0.29, p=0.034) while CD27-IgD+ was higher (r=0.29, p=0.038). Our data provide evidence that under the same medication, the immune phenotype and change over time differs in lymphopenic versus non-lymphopenic patients. Close monitoring of PBMC subtypes, may provide more information for identifying non-responders or patients who are at higher risk of developing side effects such as opportunistic infections.
Disclosure: M. Nakhaei-Nejad has nothing to disclose.
D. Barilla has nothing to disclose.
Chieh-Hsin Lee has nothing to disclose.
G. Blevins served on the scientific advisory board of Biogen, Teva, Novartis, Genzyme, Roche, and EMD Serono/Merck; received travel funding from Bio- gen, Teva, Novartis, Genzyme, Roche, and EMD Serono/Merck; consulted for Biogen, Teva, Novartis, Genzyme, Roche, and EMD Serono/Merck; and received research support from the Canadian Institutes of Health Research, Alberta Innovates, the Canadian Foundation for Innovation, and the Multiple Sclerosis Society of Canada.
F. Giuliani served on the scientific advisory board of Alberta MS Network; received speaker honoraria from Merck Serono, Biogen, Genzyme, and Roche; consulted for Merck Serono, Biogen, Genzyme, and Roche; and received research support from Biogen Canada and Alberta Ministry of Innovation and Advanced Education.

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