In vivo adsorption of autoantibodies in myasthenia gravis using Nanodisc-incorporated acetylcholine receptor.
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.
Sheng
Jian Rong
JR
Department of Neurology and Rehabilitation, College of Medicine, University of Illinois, Chicago, IL 60612, USA.
Grimme
Steve
S
Bhattacharya
Palash
P
Stowell
Michael H B
MH
Artinger
Michael
M
Prabahakar
Bellur S
BS
Meriggioli
Matthew N
MN
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
D001323:Autoantibodies; D011950:Receptors, Cholinergic