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

OBJECTIVE To evaluate the influence of dimethyl fumarate (DMF, Tecfidera) treatment of multiple sclerosis (MS) on leukocyte and lymphocyte subsets. METHODS 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. RESULTS Total leukocyte and lymphocyte counts diminished after 6 months of DMF therapy. At 12 months, lymphocyte counts had decreased by 50.1% (p < 0.0001) and were below the lower limit of normal (LLN) in one-half of patients. CD3(+) T lymphocyte counts fell by 44.2% (p < 0.0001). Among subsets, CD8(+) T cell counts declined by 54.6% (p < 0.0001), whereas CD4(+) T cell counts decreased by 39.2% (p = 0.0006). This disproportionate reduction of CD8(+) T cells relative to CD4(+) T cells was significant (p = 0.007) and was reflected by a 35.5% increase in the CD4/CD8 ratio (p = 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% (p = 0.035). Eosinophil levels decreased by 54.1% (p = 0.006), whereas levels of neutrophils, monocytes, basophils, and NK cells were not significantly altered. CONCLUSION 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.