Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients.

Area of Science:

• Immunology
• Neuroimmunology
• Pharmacology

Background:

• Dimethyl fumarate (DMF) is a treatment for multiple sclerosis (MS) that affects circulating immune cells.
• A subset of MS patients treated with DMF develops lymphopenia, characterized by a low lymphocyte count.

Purpose of the Study:

• To investigate the phenotypic changes in circulating leukocytes in MS patients undergoing DMF treatment.
• To compare immune cell profiles between lymphopenic, non-lymphopenic, and untreated MS patients, as well as healthy controls.

Main Methods:

• Cross-sectional observational study using flow cytometry to immunophenotype peripheral blood leukocytes.
• Analysis included DMF-treated lymphopenic (n=17) and non-lymphopenic (n=24) MS patients, untreated MS patients (n=17), and healthy controls (n=23).
• Longitudinal samples from 13 DMF-treated patients were also analyzed.

Main Results:

• Lymphopenic DMF-treated patients showed significantly reduced levels of CD8(+) and CD4(+) T cells, CD56(dim) NK cells, CD19(+) B cells, and plasmacytoid dendritic cells compared to controls.
• DMF treatment led to a reduction in circulating central and effector memory T cells, with a concurrent expansion of naïve T cells, irrespective of lymphopenia.
• The proportion of T-regulatory cells remained unchanged, while CD56(hi) NK cells, monocytes, and myeloid dendritic cells were unaffected by DMF.

Conclusions:

• DMF alters T cell immunophenotypes by decreasing memory cells and increasing naïve cells, potentially explaining its mechanism of action in MS.
• The disproportionate reduction of CD8(+) T cells in lymphopenic patients may compromise immunocompetence.
• These findings highlight DMF's impact on adaptive and innate immune cell populations in MS patients.