Lipoprotein receptor-related protein 4 autoantibodies in myasthenia gravis: Where are we and where are we going?

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction that leads to fatigue of skeletal muscles and fluctuating weakness. The pathogenesis of MG is sufficiently diverse to include autoimmune mechanisms. In most patients with MG, autoantibodies against acetylcholine receptor can be detected. In a smaller proportion of patients without anti-acetylcholine receptor antibodies, autoantibodies to muscle-specific kinase and low-density lipoprotein receptor-related protein 4 (LRP4) are present. LRP4 is critical for neuromuscular junction formation and maintenance. A multimolecular complex is formed among agrin, LRP4 and muscle-specific kinase that is critical for agrin signaling. The presence of anti-LRP4 antibodies is associated with mild symptoms of MG, while thymomas are rarely observed in association with MG and LRP4 antibodies. We review recent findings on the pathogenesis, clinical features and treatment of LRP4 MG.