Anti-Aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica. Tradtrantip L , Zhang H , Saadoun S , Phuan PW , Lam C , Papadopoulos MC , Bennett JL , Verkman AS . Source Departments of Medicine and Physiology, University of California, San Francisco, CA
Hua Zhang PhD 1 , Jeffrey L. Bennett MD, PhD 2 , A. S
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of spinal cord and optic nerve caused by pathogenic autoantibodies (NMO-IgG) against astrocyte aquaporin-4 (AQP4). We developed a high-throughput screen to identify blockers of NMO-IgG binding to human AQP4 using a human recombinant monoclonal NMO-IgG and transfected Fisher rat thyroid cells stably expressing human M23-AQP4
Objective: To study antibody-independent contributions of B cells to inflammatory disease activity, and the immune consequences of B-cell depletion with rituximab, in patients with multiple sclerosis (MS).Methods: B-Cell effector-cytokine responses were compared between MS patients and matched controls using a 3-signal model of activation. The effects of B-cell depletion on Th1/Th17 CD4 and CD8 T-cell responses in MS patients were assessed both ex vivo and in vivo, together with pharmacokinetic/pharmacodynamic studies as part of 2 rituximab clinical trials in relapsing–remitting MS.Results: B Cells of MS patients exhibited aberrant proinflammatory cytokine responses, including increased lymphotoxin (LT):interleukin-10 ratios and exaggerated LT and tumor necrosis factor (TNF) secretion, when activated in the context of the pathogen-associated TLR9-ligand CpG-DNA, or the Th1 cytokine interferon-y, respectively
Neuromyelitis optica is a severe, inflammatory, demyelinating disease of the central nervous system characterized by attacks of myelitis and optic neuritis.