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• W2317756537 abstract "Objective: The goal of this study was to assess the immunomodulatory in vitro effects of laquinimod on B cells from patients with relapsing-remitting multiple sclerosis (RRMS). Background The benefit of B cell-depleting therapy and other lines of evidence have emphasized a role of B cells in MS. Laquinimod is a novel orally administered drug under development for the treatment of MS, whose mode of action is not fully elucidated. Clinical data so far suggest that laquinimod is safe, well-tolerated and efficacious in reducing MRI measures of disease activity, clinical relapses and slowing the progression of disability. Design/Methods: B cells from naive MS patients were cultured with or without 1uM laquinimod for 24hrs, and analyzed by FACS for known B cell markers. B cells and CD4+ T cells from naive RRMS patients were co-cultured with or without 1uM laquinimod for 72hrs, under stimulation by CD3/CD28 and PMA+ionomycin, and cytokine levels in both B and T cells, and T cell proliferation assessed by FACS. Results: Laquinimod increased the percentage of both CD86+ and IL10+ cells within the CD25+ B cell subset, all markers associated with B cell regulatory functions. The CD25+ B cells demonstrated their regulatory capacity by reducing proliferation of T cells and the percentage of IFNg+ T cells. Laquinimod-treated B cells reduced the expression of IFNg and of IL4 and increased the expression of IL10 and TGFb in T cells, in a B-cell mediated manner. Laquinimod also reduced the expression of IL4, induced IL10 and TGFb expression in B cells in the co-culture, and decreased the percentage of IFNg+ T cells in T cells alone. Conclusions: Laquinimod modulates B cell characteristics and regulatory functions, affecting B cell cytokine and B cell-mediated- T cell cytokine profile, which may be part of the beneficial mode of action of laquinimod in MS patients. Supported by: Financial support from Teva Pharmaceuticals. Disclosure: Dr. Miller has received personal compensation for activities with Teva Pharmaceutical Industries Ltd., Medison Pharma Ltd., Biogen Idec, Merck Serono, Avanir Pharmaceuticals, Novartis, and Bayer Schering Pharma. Dr. Miller has received research support from Teva Pharmaceutical Industries Ltd., Medison Pharma Ltd., Biogen Idec, Merck Serono, and Bayer Schering Pharma. Dr. Nussbaum has nothing to disclose. Dr. Staun-Ram has received research support from Teva Pharmaceuticals. Dr. Snir has nothing to disclose. Dr. Hayardeny Nisimov has nothing to disclose. Dr. Melamed has received research support from Teva Neuroscience. Dr. Toubi has received research support from Teva Pharmaceuticals." @default.
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• W2317756537 date "2012-04-22" @default.
• W2317756537 modified "2023-09-23" @default.
• W2317756537 title "Laquinimod-Mediated Modulation of B Cells from Multiple Sclerosis Patients: Affecting Direct and Indirect Immune-Regulatory Functions (P02.116)" @default.
• W2317756537 doi "https://doi.org/10.1212/wnl.78.1_meetingabstracts.p02.116" @default.
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