IFNbeta-1b Treatment Alters the Composition of Circulating B Cell Subsets, in Particular Reducing the Number of Autoantibody Secreting B1 Cells in Patients with Relapsing-Remitting Multiple Sclerosis (P02.086)

Objective: The hypothesis tested is that B cell subsets in RRMS patients differ from healthy controls and that treatment with IFN-1b alters these subsets. Background Therapy directed at the depletion of CD20+ B cells has been shown in Phase II clinical trials to be effective in reducing relapse rate and improving MRI in those with RRMS. A subset of human autoantibody producing cells, B1 cells, has recently been described. B1 cells present antigen efficiently and induce naive CD4 T cells to become Th17 cells, a major pro-inflammatory compartment that is involved in the pathogenesis of human RRMS. These cells are found in low frequency in peripheral blood and are CD20+CD27+CD43+. This study investigates the phenotype of B cells from patients pre- and post-treatment with IFNbeta-1b. Design/Methods: Blood was drawn from 10 healthy donors and from 10 RRMS patients before treatment and again 2 and 6 months after daily injections of IFNbeta-1b. Cryopreserved PBMCs were thawed and stained with panels of antibodies against B cell surface antigens. Results: At baseline, RRMS patients have increased frequencies of CD19+CD20+ B cells and decreased frequencies of memory B cells. Notably, those with RMS have a 2-to-3-fold higher frequency of B1 cells compared to healthy controls at baseline. B1 cells from RRMS patients express more CD5 when compared with healthy controls. In response to treatment with IFNbeta-1b, the number of circulating B1 cells declines. Conclusions: This study demonstrates an increased frequency in the number of circulating B cells that carry a phenotype consistent with autoantibody-producing B1 cells in those with RRMS. This population of cells is reduced in response to treatment with IFNbeta-1b. Although the number of subjects in this study was limited, these findings suggest that this B1 population may be linked to an increase in disease activity. Supported by: Bayer HealthCare Pharmaceuticals Inc. Disclosure: Dr. Mielcarz has nothing to disclose. Dr. Bergeron has nothing to disclose. Dr. DeLong has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Heyn has nothing to disclose. Dr. Mack has nothing to disclose. Dr. Conrad has nothing to disclose. Dr. Oliver has nothing to disclose. Dr. Kasper has received personal compensation for activities with Teva Neuroscience, Serono, Inc., Bayer Pharmaceuticals Corporation, Genentech, Inc., Mederex as a consultant and participant on a scientifc advisory board. Dr. Kasper has received research support from Teva Neuroscience, Serono, Inc. and Bayer Pharmaceutical Corporation. Dr. Channon has nothing to disclose.