Suppressed Pro-Inflammatory Properties Of Circulating B Cells In Patients With Multiple Sclerosis Treated With Fingolimod, Based On Altered Proportions Of B-Cell Subpopulations (P1.198)

OBJECTIVE: To elucidate the effect of fingolimod on circulating B cells of multiple sclerosis (MS) patients. BACKGROUND: The chief mechanism by which fingolimod exerts its effect in MS is considered to be sequestration of pathogenic lymphocytes into secondary lymphoid tissues. However, this effect of fingolimod on lymphocytes seems to differ among lymphocyte subsets. B cells have recently been recognized as important immune regulators in MS through their antibody-independent activities such as cytokine production and antigen presentation to T cells. Although circulating B-cell levels are reportedly reduced in patients treated with fingolimod, the detailed effect of fingolimod on human B cells is unknown. DESIGN/METHODS: Peripheral blood mononuclear cells were obtained from 17 untreated MS patients, 15 MS patients treated with fingolimod (MS-F), and 11 healthy controls. The number and percentage of B cells and their subsets, and expression of costimulatory molecules on B cells were analyzed by flow cytometer. Tumor necrosis factor (TNF)α and interleukin (IL)-10 production from B cells in response to phorbol myristate acetate, ionomycin, and CpG DNA was assessed by flow cytometer. RESULTS: MS-F had a significantly lower number of B cells in the circulation. The remaining B cells in the blood of MS-F had a reduced proportion of memory and an increased that of naive B-cell populations, expressed lower levels of the costimulatory molecule CD80, and produced less TNFα and more IL-10. The alteration in the cytokine profile of B cells from MS-F was based on an increased proportion of the transitional B-cell subpopulation within the naive B-cell compartment. CONCLUSIONS: Together with the reduction in the number of B cells in the circulation, the observed alteration in the cytokine profile and reduced expression of the costimulatory molecule in B cells of MS-F might be related to the therapeutic effect of this drug in MS. Disclosure: Dr. Miyazaki has received personal compensation for activities with Novartis and Biogen Idec. Dr. Niino has received personal compensation for activities with Biogen Idec, Bayer Schering, Asahi Kasei Kuraray Medical Co., and Novartis. Dr. Fukazawa has received personal compensation for activities with Bayer Schering, Biogen Idec, Mitsubishi Tanabe Pharma Corporation, and Novartis. Dr. Takahashi has nothing to disclose. Dr. Nonaka has nothing to disclose. Dr. Amino has nothing to disclose. Dr. Tashiro has nothing to disclose. Dr. Minami has nothing to disclose. Dr. Fujiki has nothing to disclose. Dr. Doi has nothing to disclose. Dr. Kikuchi has received personal compensation for activities with Novartis, Boehringer Ingelheim Pharmaceuticals Inc., Kyowa Hakko Kirin, Dainippon Sumitomo Pharma, and FP Pharmaceutical Corporation.