title: Discovering novel targets for autoantibodies in dilated cardiomyopathy.
abstract: There is increasing evidence that a large proportion of dilated cardiomyopathy (DCM) cases are mediated by autoimmune processes. Since DCM is a fatal disorder with rapid aggravation and is the leading cause of heart transplantation, further insights into disease pathogenesis are needed. Recent studies have separated the pathogenic capacity of autoantibodies and initial clinical trials removing such autoantibodies via immunoadsorption have been promising. In order to elucidate the full autoantibody repertoire involved in DCM, we applied an autoantibody screening test using ventricular and atrial proteomes as autoantigenic sources and subsequently tested the autoantibody-binding patterns of sera from dogs with spontaneous DCM. With this method, we detected five potentially DCM-related autoantigens which were identified by MS as being: myosin heavy chain cardiac muscle alpha isoform, alpha cardiac actin, mitochondrial aconitate hydratase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and brain glycogen phosphorylase (GPBB). The recovery of two known DCM autoantigens (myosin heavy chain and alpha cardiac actin) and the discovery of three novel autoantigens (mitochondrial aconitate hydratase, GADPH, and GPBB) underscore the efficacy of this experimental method and the significance of the spontaneous canine DCM model.
authors.affiliation: Institute of Animal Physiology, Ludwig Maximilians University, Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Buse
authors.forename: Frank
authors.initials: F
authors.lastname: Altmann
authors.forename: Barbara
authors.initials: B
authors.lastname: Amann
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Hauck
authors.forename: Cordula
authors.initials: C
authors.lastname: Poulsen Nautrup
authors.forename: Marius
authors.initials: M
authors.lastname: Ueffing
authors.forename: Manfred
authors.initials: M
authors.lastname: Stangassinger
authors.forename: Cornelia A
authors.initials: CA
authors.lastname: Deeg
mesh_terms: D000154:Aconitate Hydratase / Q000276:immunology; D000199:Actins / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000032:analysis*; D015153:Blotting, Western / Q000379:methods; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000662:veterinary*; D004283:Dog Diseases / Q000276:immunology*; D004285:Dogs; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000276:immunology; D025002:Glycogen Phosphorylase, Brain Form / Q000276:immunology; D024723:Ventricular Myosins / Q000276:immunology
chemical_list: D000199:Actins; D001323:Autoantibodies; D001324:Autoantigens; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D025002:Glycogen Phosphorylase, Brain Form; D024723:Ventricular Myosins; D000154:Aconitate Hydratase