Dimethyl fumarate induces changes in B- and T-lymphocyte function independent of the effects on absolute lymphocyte count
Document Type
Article
Abstract
BACKGROUND: Dimethyl fumarate (DMF) is used to treat relapsing multiple sclerosis and causes lymphopenia in a subpopulation of treated individuals. Much remains to be learned about how the drug affects B- and T-lymphocytes. OBJECTIVES: To characterize changes in B- and T-cell phenotype and function induced by DMF and to investigate whether low absolute lymphocyte count (ALC) is associated with unique functional changes. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from DMF-treated patients, untreated patients, and healthy controls. A subset of DMF-treated patients was lymphopenic (ALC < 800). Multiparametric flow cytometry was used to evaluate cellular phenotypes. Functional response to non-specific and viral peptide stimulation was assessed. RESULTS: DMF reduced circulating memory B-cells regardless of ALC. Follicular T-helper cells (CD4 CXCR5) and mucosal invariant T-cells (CD8 CD161) were also reduced. DMF reduced T-cell production of pro-inflammatory cytokines in response to polyclonal (PMA/ionomycin) and viral peptide stimulation, regardless of ALC. No differences in activation-induced cell death or circulating progenitors were observed between lymphopenic and non-lymphopenic DMF-treated patients. CONCLUSION: These data implicate DMF-induced changes in lymphocytes as an important component of the drug's efficacy and expand our understanding of the functional significance of DMF-induced lymphopenia.
Keywords
Dimethyl fumarate, disease-modifying therapy, immunology, multiple sclerosis
Medical Subject Headings
Adult; B-Lymphocytes (drug effects); Cross-Sectional Studies; Dimethyl Fumarate (therapeutic use); Female; Humans; Immunosuppressive Agents (therapeutic use); Lymphocyte Count; Lymphopenia (chemically induced); Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting (drug therapy, immunology); T-Lymphocytes (drug effects)
Publication Date
5-1-2018
Publication Title
Multiple sclerosis (Houndmills, Basingstoke, England)
E-ISSN
1477-0970
Volume
24
Issue
6
First Page
728
Last Page
738
PubMed ID
28480794
Digital Object Identifier (DOI)
10.1177/1352458517707069
Recommended Citation
Longbrake, Erin E.; Cantoni, Claudia; Chahin, Salim; Cignarella, Francesca; Cross, Anne H.; and Piccio, Laura, "Dimethyl fumarate induces changes in B- and T-lymphocyte function independent of the effects on absolute lymphocyte count" (2018). Translational Neuroscience. 2328.
https://scholar.barrowneuro.org/neurobiology/2328