title: Specific removal of beta1-adrenoceptor autoantibodies by immunoabsorption in rabbits with autoimmune cardiomyopathy improved cardiac structure and function.
abstract: Growing evidence suggests that the beta1-adrenoceptor-directed autoimmune mechanism may play an important role in the pathogenesis of idiopathic dilated cardiomyopathy. The aim of this study is to further study the effect of specific immunoabsorption of anti-beta1-adrenoceptor autoantibodies on cardiac structure and function in autoimmune cardiomyopathy in rabbits. Twenty-four male rabbits were divided into 2 groups: (1) one immunized with beta1-adrenoceptor peptide (beta1 group, n=16), and (2) the other receiving saline injection as a control (control group, n=8). Immunization was performed once a month for 8 months. A high concentration of anti-beta1-adrenoceptor autoantibodies was exhibited throughout the immunization period. Rabbits in the beta1 group showed increased left ventricular end-diastolic diameter (LVDd), decreased left ventricular ejection fraction (LVEF) and increased LV mass/body weight ratio after the 8th month. Immunoabsorption with beta1-adrenoceptor peptide column was able to remove up to 35% of anti-beta1-adrenoceptor autoantibodies in 2 h, resulting in decreased LVDd and increased LVEF 3 months after. Specific removal of anti-beta1-adrenoceptor autoantibodies improved cardiac structure and function in experimental autoimmune cardiomyopathy. These results suggest that anti-beta1-adrenoceptor autoantibodies are of pathogenic importance in the induction of cardiomyopathy, and that specific immunoabsorption as an emerging therapy may be considered when anti-beta1-adrenoceptor autoantibodies are pathophysiologically involved.
authors.affiliation: Department of Cardiology, Kanazawa Medical University, 1-1, Daigaku, Uchinada, Ishikawa, Japan. matsui@kanazawa-med.ac.jp
authors.forename: Shinobu
authors.initials: S
authors.lastname: Matsui
authors.forename: Lisa
authors.initials: L
authors.lastname: Larsson
authors.forename: Mituru
authors.initials: M
authors.lastname: Hayase
authors.forename: Shogo
authors.initials: S
authors.lastname: Katsuda
authors.forename: Kohei
authors.initials: K
authors.lastname: Teraoka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kurihara
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Murano
authors.forename: Katsuzou
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Michael
authors.initials: M
authors.lastname: Fu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000302:isolation & purification*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D001835:Body Weight; D009202:Cardiomyopathies / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D004562:Electrocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D006321:Heart / Q000502:physiology*; D007163:Immunosorbent Techniques; D007167:Immunotherapy; D008297:Male; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009206:Myocardium / Q000737:chemistry / Q000648:ultrastructure; D009929:Organ Size; D011817:Rabbits; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D018342:Receptors, Adrenergic, beta-1