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Increased NK Cell Count in Multiple Sclerosis Patients Treated With Dimethyl Fumarate: A 2-Year Longitudinal Study
Damiano Marastoni1, Alessandro Buriani2, Anna Isabella Pisani1
1Neurology B, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Abstract:
Background: Dimethyl fumarate (DMF) is a disease-modifying drug for relapsing-remitting multiple sclerosis. Among others, DMF impedes immune activation by shifting the balance between inflammatory and regulatory cell types and by inducing apoptosis-triggered lymphopenia. Although the decrease in lymphocyte count is an early effect of the drug in several patients, the long-term impact on lymphocyte subsets is largely unknown. Methods: We performed a 2-years observational study on total lymphocyte count and subsets thereof by flow cytometry of peripheral blood of 38 multiple sclerosis patients in treatment with DMF. Data were collected at the beginning and after 3, 6, 12, and 24 months of therapy. Results: Total lymphocyte count decreased in relation to time of exposure to DMF. Mean absolute B cell count decreased by 34.1% (p < 0.001) within the first 3 months of therapy and then remained stable over time. Mean absolute CD3+ T cells count decrement reached 47.5% after 12 months of treatment (p < 0.001). NK cells count showed a heterogeneous trend, increasing by 85.9% (p < 0.001) after 2 years of treatment. CD4+ T cells and CD8+ T cells substantially decreased, with a significant increase of CD4+/CD8+ ratio during the first year of therapy. Conclusions: NK cells showed a heterogeneous behavior during DMF treatment with a significant increase over time. Since NK cells may also have a regulatory effect on immune system modulation, their increase during DMF treatment might play a role in the efficacy and safety of the drug.
Insights
Dimethyl fumarate (DMF) treatment for multiple sclerosis causes a decrease in B and T cells but a significant increase in Natural Killer (NK) cells over two years, potentially impacting drug efficacy.
Area of Science:
- Immunology
- Neurology
- Pharmacology
Background:
- Dimethyl fumarate (DMF) is a key disease-modifying therapy for relapsing-remitting multiple sclerosis.
- DMF modulates immune responses by altering immune cell populations and inducing lymphopenia.
- The long-term effects of DMF on specific lymphocyte subsets remain incompletely understood.
Purpose of the Study:
- To investigate the long-term impact of dimethyl fumarate (DMF) on lymphocyte subsets in multiple sclerosis (MS) patients.
- To analyze changes in total lymphocyte count and specific subsets over a 24-month treatment period.
Main Methods:
- A 2-year observational study involving 38 multiple sclerosis patients treated with DMF.
- Flow cytometry was used to analyze peripheral blood lymphocyte counts and subsets at baseline and at 3, 6, 12, and 24 months.
- Statistical analysis was performed to assess changes over time.
Main Results:
- Total lymphocyte counts decreased with DMF exposure.
- Significant reductions were observed in B cells (34.1%) and T cells (CD3+, CD4+, CD8+) within 12 months.
- Natural Killer (NK) cell counts showed a significant increase (85.9%) after 2 years, with a notable rise in the CD4+/CD8+ ratio during the first year.
Conclusions:
- Dimethyl fumarate (DMF) treatment leads to a sustained decrease in B and T lymphocytes but a significant increase in Natural Killer (NK) cells over two years.
- The observed increase in NK cells may contribute to the immunomodulatory effects and therapeutic benefits of DMF in multiple sclerosis.
- Understanding these long-term lymphocyte dynamics is crucial for evaluating DMF's efficacy and safety profile.
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