Journal
JOURNAL OF THE NEUROLOGICAL SCIENCES
Volume 398, Issue -, Pages 4-8Publisher
ELSEVIER
DOI: 10.1016/j.jns.2019.01.007
Keywords
Multiple sclerosis; Dimethyl fumarate; Risk factors; Lymphopenia; Lymphocyte subsets
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Funding
- Fondo para la Investigacion Sanitaria [PI15/00513, RD16/0015/0001]
- Instituto de Salud Carlos III. Ministerio de Economia y Competitividad. Spain
- FEDER
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Background: Lymphopenia is a major concern in MS patients treated with dimethyl-fumarate (DMF) as it increases the risk of progressive multifocal leukoencephalopathy. Objective: To identify factors associated with lymphopenia in DMF-treated patients and explore changes in blood lymphocyte subsets associated with DMF-induced lymphopenia. Methods: Prospective longitudinal study including 106 patients initiating DMF treatment followed for a median time of 24.67 months. Blood lymphocyte subsets were studied in 64 patients by flow cytometry at baseline and 6 months after. Results: Mean absolute lymphocyte counts (ALCs) decreased by 29% during the first year of DMF-treatment. Patients developing lymphopenia showed a faster decline within the three first months. A reduction of ALCs higher than 38% at this time was associated to subsequent development of grade 2-3 lymphopenia (OR = 5.93, 95% CI: 1.9-18.6, p = 0.002). All patients showed a significant decrease in different T and B lymphocyte subsets upon DMF therapy. In addition, lymphopenic patients experienced a selective decrease in natural killer T (NKT) cell percentages (p = 0.01), and a high drop in NKT total counts (p < 0.0001). Conclusions: Patients who experience a drop in ALCs by > 38% at three months of DMF-treatment are about 6 times more likely to develop significant lymphopenia. This decrease is clearly associated with a considerable loss of NKT cells.
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