Treatment of MS patients with BG-12 results in a decline in circulating memory T and B lymphocytes (HUM1P.317)

Abstract

Abstract BG-12 (Tecfidera®) is a recently approved oral treatment for multiple sclerosis that has shown remarkable efficacy. The mechanisms by which BG-12 acts on the human immune system are poorly defined. In the current study, we analyzed the effects of BG-12 treatment on subsets of circulating human T and B lymphocytes using multicolor flow cytometry. Patients treated for four months with BG-12 had decreased total numbers of lymphocytes in their blood that did not reach significance, and no changes in their overall percentages of CD4+ T cells, CD8+ T cells, or CD19+ B cells compared to pretreatment levels. Significant differences were observed when subsets of T and B cells were evaluated. BG-12 treatment resulted in a decrease in percentages of circulating CD4+CD45RO+CD45RAneg memory TH cells and CD8+CD45RO+CD45RAneg memory CTL. Treatment with BG-12 also resulted in significant decreases in circulating CD27+CD19+ memory B cells, and a relative increase in the levels of CD24highCD38highCD19+ regulatory B cells. A CD27+CD24lowCD19+ B cell subset was present in the circulation of some MS patients prior to treatment, but returned to the very low levels found in healthy controls following four months of BG-12 treatment. The data suggest that BG-12 has in vivo down regulatory effects on some lymphocyte subsets, particularly memory T and B cells. Ongoing experiments are focused on measuring functional differences in T and B cell cytokine production in BG-12 treated patients.