Clinical pictures and neuromuscular junction pathomechanism in novel LDL- recepotr related protein 4 antibody-positive myasthenia gravis

点击翻译按钮获取中文摘要

Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission mediated by pathogenic autoantibodies (Abs) against acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK). The seropositivity rates for routine AChR binding Ab and MuSK Ab in MG are 80-85% and 5-10% for MG patients in Japan, respectively. In 2011, autoantibodies against low-density lipoprotein receptor-related protein 4 (Lrp4) were identified in Japanese MG patients. We developed a simple technique termed Gaussia luciferase immunoprecipitation for detecting antibodies to Lrp4. As a result, nine generalized MG patients from 300 lacking AChR Ab are positive for Lrp4 antibodies. These antibodies inhibit binding of Lrp4 to its ligand and are predominantly of the IgG1 subclass. Further studies including neuromuscular junction biopsy are needed to clarify the pathomechanism of Lrp4 ab positive MG. These results indicate that Lrp4 is a third pathogenic autoantigen in patients with MG.