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

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.

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