Reduction of CD8 ⁺ T lymphocytes in multiple sclerosis patients treated with dimethyl fumarate

Abstract

<h3>Objective:</h3> To evaluate the influence of dimethyl fumarate (DMF, Tecfidera) treatment of multiple sclerosis (MS) on leukocyte and lymphocyte subsets. <h3>Methods:</h3> Peripheral blood leukocyte and lymphocyte subsets, including CD3⁺, CD4⁺, and CD8⁺ T cells; CD19⁺ B cells; and CD56⁺ natural killer (NK) cells, were obtained at baseline and monitored at 3 months, 6 months, and 12 months after initiation of DMF treatment. <h3>Results:</h3> Total leukocyte and lymphocyte counts diminished after 6 months of DMF therapy. At 12 months, lymphocyte counts had decreased by 50.1% (<i>p</i> &lt; 0.0001) and were below the lower limit of normal (LLN) in one-half of patients. CD3⁺ T lymphocyte counts fell by 44.2% (<i>p</i> &lt; 0.0001). Among subsets, CD8⁺ T cell counts declined by 54.6% (<i>p</i> &lt; 0.0001), whereas CD4⁺ T cell counts decreased by 39.2% (<i>p</i> = 0.0006). This disproportionate reduction of CD8⁺ T cells relative to CD4⁺ T cells was significant (<i>p</i> = 0.007) and was reflected by a 35.5% increase in the CD4/CD8 ratio (<i>p</i> = 0.007). A majority of CD8⁺ T cell counts, but not CD4⁺ T cell counts, were below the LLN even when total lymphocyte counts were greater than 500 cells/μL. CD19⁺ B cell counts were reduced by 37.5% (<i>p</i> = 0.035). Eosinophil levels decreased by 54.1% (<i>p</i> = 0.006), whereas levels of neutrophils, monocytes, basophils, and NK cells were not significantly altered. <h3>Conclusion:</h3> Subsets of peripheral blood leukocytes and lymphocytes are differentially affected by DMF treatment of MS. Reduction of CD8⁺ T cells is more pronounced than that of CD4⁺ T cells. These findings may have implications for cell-mediated antiviral immunity during DMF treatment.