ENAGenomicsGladstone Instituteshttps://www.ebi.ac.uk/ena/browser/view/PRJNA487343Mus musculusActivation of innate immunity and deposition of blood-derived fibrin in the central nervous system (CNS) occur in autoimmune and neurodegenerative diseases, including multiple sclerosis (MS) and Alzheimer’s disease (AD). However, mechanisms linking blood-brain barrier (BBB) disruption with neurodegeneration are poorly understood, and exploration of fibrin as a therapeutic target has been limited by its beneficial clotting functions. Here we report the generation of monoclonal antibody 5B8 targeted against the cryptic fibrin epitope γ377-395 to selectively inhibit fibrin-induced inflammation. 5B8 suppressed fibrin-induced proinflammatory gene expression, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, and oxidative stress. In animal models of MS and AD, 5B8 entered the CNS and bound to parenchymal fibrin, and its therapeutic administration reduced innate immune activation and neurodegeneration without interfering with clotting. Thus, fibrin-targeting immunotherapy inhibits autoimmune- and amyloid-driven neurotoxicity and may have clinical benefit without globally suppressing innate immunity or interfering with coagulation in diverse neurological diseases. Overall design: Mouse macrophages were stimulated for 6 hr with fibrin in the presence of 5B8 or isotype control IgG2b and subjected for RNA extraction and hybridization on Affymatrix microarrays. Data are from three independent biological replicates.xref:PubMed:30323343ENAIgG Antibody, data, Controlling, preventive therapy, Immunoglobulin, Monocyte Derived Macrophages, Monocyte Derived, B-cell receptor complex, antibodies, Fibrins, antibody, Monocyte-Derived, Antibody, BCR complex, IgG3, IgG4, IgG1, Gamma Globulin, IgG2, Monocyte-Derived Macrophage, immunoglobulin complex, prevention and control, Antithrombin I, Monocyte-Derived Macrophages, Macrophage, opsonin activity, IgG, reference sample, Immunoglobulin GT, IgG(T), Macrophages, membrane bound, IgG2a, IgG2b, prophylaxis, IgG2c, Polyglobin, Bone Marrow Derived Macrophages, prevention., Bone Marrow-Derived Macrophage, Bone Marrow-Derived, preventive measures, immunoglobulin, B cell receptor accessory molecule complex, control, IgG2A, IgG2B, GT, B lymphocyte receptor complex, Bone Marrow-Derived Macrophages, 7S Gamma Globulin, B cell receptor activity, Allerglobuline, B-lymphocyte receptor complex, 7S, ControlledIgG Antibody, data, Controlling, preventive therapy, Immunoglobulin, Monocyte Derived Macrophages, Monocyte Derived, B-cell receptor complex, antibodies, Fibrins, antibody, Monocyte-Derived, Antibody, BCR complex, IgG3, IgG4, IgG1, Gamma Globulin, IgG2, Monocyte-Derived Macrophage, immunoglobulin complex, prevention and control, Antithrombin I, Monocyte-Derived Macrophages, Macrophage, opsonin activity, IgG, reference sample, Immunoglobulin GT, IgG(T), Macrophages, membrane bound, IgG2a, IgG2b, prophylaxis, IgG2c, Polyglobin, Bone Marrow Derived Macrophages, prevention., Bone Marrow-Derived Macrophage, Bone Marrow-Derived, preventive measures, immunoglobulin, B cell receptor accessory molecule complex, control, IgG2A, IgG2B, GT, B lymphocyte receptor complex, Bone Marrow-Derived Macrophages, 7S Gamma Globulin, B cell receptor activity, Allerglobuline, B-lymphocyte receptor complex, 7S, ControlledfalseExpression data from fibrin-stimulated macrophages treated with 5B8 antibody or IgG2b controlExpression data from fibrin-stimulated macrophages treated with 5B8 antibody or IgG2b control2025-09-242019-02-15PRJNA487343GSE1189211009030323343