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

Abstract

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 CD31, CD41, and CD81 T cells; CD191 B cells; and CD561 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. CD31 T lymphocyte counts fell by 44.2% (p < 0.0001). Among subsets, CD81 T cell counts declined by 54.6% (p < 0.0001), whereas CD41 T cell counts decreased by 39.2%(p = 0.0006). This disproportionate reduction of CD81 T cells relative to CD41 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 CD81 T cell counts, but not CD41 T cell counts, were below the LLN even when total lymphocyte counts were greater than 500 cells/mL. CD191 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 CD81 T cells is more pronounced than that of CD41 T cells. These findings may have implications for cell-mediated antiviral immunity during DMF treatment.