title: Autoantibody depletion ameliorates disease in murine experimental autoimmune encephalomyelitis.
abstract: Much data support a role for central nervous system antigen-specific antibodies in the pathogenesis of multiple sclerosis (MS). The effects of inducing a decrease in (auto)antibody levels on MS or experimental autoimmune encephalomyelitis (EAE) through specific blockade of FcRn, however, remain unexplored. We recently developed engineered antibodies that lower endogenous IgG levels by competing for binding to FcRn. These Abdegs ("antibodies that enhance IgG degradation") can be used to directly assess the effect of decreased antibody levels in inflammatory diseases. In the current study, we show that Abdeg delivery ameliorates disease in an EAE model that is antibody dependent. Abdegs could therefore have promise as therapeutic agents for MS.
authors.affiliation: Department of Immunology; University of Texas Southwestern Medical Center; Dallas, TX USA.
authors.forename: Dilip K
authors.initials: DK
authors.lastname: Challa
authors.forename: Uta
authors.initials: U
authors.lastname: Bussmeyer
authors.forename: Tarique
authors.initials: T
authors.lastname: Khan
authors.forename: Héctor P
authors.initials: HP
authors.lastname: Montoyo
authors.forename: Pankaj
authors.initials: P
authors.lastname: Bansal
authors.forename: Raimund J
authors.initials: RJ
authors.lastname: Ober
authors.forename: E Sally
authors.initials: ES
authors.lastname: Ward
mesh_terms: D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology / Q000517:prevention & control; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D015202:Protein Engineering / Q000379:methods*; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D063308:Myelin-Oligodendrocyte Glycoprotein; D011961:Receptors, Fc; D011994:Recombinant Proteins; C100688:Fc receptor, neonatal
keywords: EAE; FcRn; autoantibody; engineered antibodies; therapy