title: In vivo adsorption of autoantibodies in myasthenia gravis using Nanodisc-incorporated acetylcholine receptor.
abstract: Autoantibodies directed against the skeletal muscle acetylcholine receptor (AChR) play a critical role in the pathogenesis of the autoimmune disease, myasthenia gravis (MG). The pathogenic importance of anti-AChR antibodies is substantiated clinically by the often dramatic clinical improvement that follows removal of circulating antibodies utilizing extracorporeal plasma exchange (PE). Unfortunately, the effects of PE are non-specific as immunoglobulins (IgG) and other plasma proteins are removed in addition to anti-AChR IgG. In this study, we have successfully incorporated the AChR protein purified from Torpedo californicus into a Nanodisc (ND) membrane scaffold protein/phospholipid structure. We go on to demonstrate the effectiveness of this ND-AChR complex, administered intravenously, in the in vivo down-modulation of anti-AChR antibodies and subsequent amelioration of clinical disease in the experimental murine model of MG. These results provide proof-of-principle for the in vivo antigen-specific reduction of pathogenic anti-AChR antibodies utilizing ND-AChR particles. Further development of this strategy may provide an effective, antigen-specific, and readily accessible acute therapy for exacerbating MG or myasthenic crisis.
authors.affiliation: Department of Neurology and Rehabilitation, College of Medicine, University of Illinois, Chicago, IL 60612, USA.
authors.forename: Jian Rong
authors.initials: JR
authors.lastname: Sheng
authors.forename: Steve
authors.initials: S
authors.lastname: Grimme
authors.forename: Palash
authors.initials: P
authors.lastname: Bhattacharya
authors.forename: Michael H B
authors.initials: MH
authors.lastname: Stowell
authors.forename: Michael
authors.initials: M
authors.lastname: Artinger
authors.forename: Bellur S
authors.initials: BS
authors.lastname: Prabahakar
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Meriggioli
mesh_terms: D000327:Adsorption / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D018482:Muscle, Skeletal / Q000276:immunology; D009157:Myasthenia Gravis / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D054457:Tissue Scaffolds; D014101:Torpedo
chemical_list: D001323:Autoantibodies; D011950:Receptors, Cholinergic