کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3055991 | 1186549 | 2010 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: In vivo adsorption of autoantibodies in myasthenia gravis using Nanodisc-incorporated acetylcholine receptor In vivo adsorption of autoantibodies in myasthenia gravis using Nanodisc-incorporated acetylcholine receptor](/preview/png/3055991.png)
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.
Research highlights
► The authors successfully incorporated the acetylcholine receptor (AChR) protein purified from Torpedo californicus into a Nanodisc (ND) membrane scaffold protein/phospholipid structure.
► The authors 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 myasthenia gravis (MG).
► This study provides proof-of-principle for the in vivo antigen-specific reduction of pathogenic anti-AChR antibodies utilizing ND–AChR particles, which may represent a novel strategy for the treatment of exacerbating MG.
Journal: Experimental Neurology - Volume 225, Issue 2, October 2010, Pages 320–327