title: CD19 as a therapeutic target in a spontaneous autoimmune polyneuropathy.
abstract: Spontaneous autoimmune polyneuropathy (SAP) in B7-2 knock-out non-obese diabetic (NOD) mice is mediated by myelin protein zero (P0)-reactive T helper type 1 (Th1) cells. In this study, we investigated the role of B cells in SAP, focusing on CD19 as a potential therapeutic target. We found that P0-specific plasmablasts and B cells were increased in spleens of SAP mice compared to wild-type NOD mice. Depletion of B cells and plasmablasts with anti-CD19 monoclonal antibody (mAb) led to attenuation of disease severity when administered at 5 months of age. This was accompanied by decreased serum immunoglobulin (Ig)G and IgM levels, depletion of P0-specific plasmablasts and B cells, down-regulation/internalization of surface CD19 and increased frequency of CD4(+) regulatory T cells in spleens. We conclude that B cells are crucial to the pathogenesis of SAP, and that CD19 is a promising B cell target for the development of disease-modifying agents in autoimmune neuropathies.
authors.affiliation: Department of Neurology, The University of Chicago, Chicago, IL, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Abraham
authors.forename: S H
authors.initials: SH
authors.lastname: Quan
authors.forename: D
authors.initials: D
authors.lastname: Dukala
authors.forename: B
authors.initials: B
authors.lastname: Soliven
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D015536:Down-Regulation; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D018993:Myelin P0 Protein / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D010950:Plasma Cells / Q000276:immunology; D011115:Polyneuropathies / Q000276:immunology* / Q000628:therapy*; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C560546:Mpz protein, mouse; D018993:Myelin P0 Protein
keywords: B cells; CIDP; Guillain-Barré syndrome; autoimmunity; co-stimulatory molecules