Reduction of CD8+ T lymphocytes in multiple sclerosis patients treated with dimethyl fumarate. Issue 3 (June 2015)

• Record Type: Journal Article
• Authors: Spencer, Collin M.; Crabtree-Hartman, Elizabeth C.; Lehmann-Horn, Klaus; Cree, Bruce A.C.; Zamvil, Scott S.
• Is Part Of: Neurology. Volume 2:Issue 3(2015)
• Publication Date: 2015-06
• Subjects: Neuroimmunology -- Periodicals; Neurology -- Periodicals; 616.8
• DOI: 10.1212/NXI.0000000000000076
• Languages: English
• ISSNs: 2332-7812

Abstract

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 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.