Autoimmune neurologic diseases
Background: Fingolimod is a sphingosine-1-phosphate receptor agonist used as a disease-modifying drug for multiple sclerosis (MS). We have previously shown that MS patients treated with fingolimod have an increased proportion of circulating transitional B cells, but the underlying mechanism remains unknown. B cell-activating factor of the TNF family (BAFF) is a cytokine involved in the differentiation and proliferation of B cells. Mice overexpressing BAFF have been shown to have increased numbers of transitional B cells; therefore, we hypothesized that BAFF is involved in an increase in transitional B cells in MS patients treated with fingolimod. Subjects and methods: Serum samples were collected from 25 healthy subjects, 32 untreated MS patients, and 30 MS patients treated with fingolimod. Concentrations of BAFF in serum were quantified by ELISA. In addition, alterations in serum BAFF levels after starting fingolimod were analyzed in three treatment-naïve MS patients. The proportions of B cell subsets in 14 MS patients treated with fingolimod were determined by flow cytometry, and the relationships between serum BAFF concentrations and each B cell subset were analyzed. Results: Serum concentrations of BAFF were significantly higher in fingolimod-treated MS patients than in healthy subjects or untreated MS patients (p < 0.001). Serum levels of BAFF rose significantly after starting fingolimod treatment in the longitudinal study (p=0.014). A significant positive correlation was found between the serum concentration of BAFF and the percentage of transitional B cells (p=0.0244). Conclusion: BAFF is involved in the increase in circulating transitional B cells in MS patients treated with fingolimod.