Division of Genetics, Department of Cancer Biology, the Institute of Medical Science, the University of Tokyo, Japan.
Ann Neurol. 2011 Feb;69(2):418-22. doi: 10.1002/ana.22312.
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction, where acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and low-density lipoprotein (LDL) receptor-related protein 4 (Lrp4) are essential. About 80% and 0% to 10% of patients with generalized MG have autoantibodies to AChR and MuSK, respectively, but pathogenic factors are elusive in others. Here we show that a proportion of AChR antibody-negative patients have autoantibodies to Lrp4. These antibodies inhibit binding of Lrp4 to its ligand and predominantly belong to the immunoglobulin G1 (IgG1) subclass, a complement activator. These findings together indicate the involvement of Lrp4 antibodies in the pathogenesis of AChR antibody-negative MG.
重症肌无力（MG）是一种神经肌肉接头的自身免疫性疾病，其中乙酰胆碱受体（AChR）、肌肉特异性激酶（MuSK）和低密度脂蛋白受体相关蛋白 4（Lrp4）是必不可少的。约 80%和 0%至 10%的全身性 MG 患者分别具有针对 AChR 和 MuSK 的自身抗体，但其他患者的致病因素尚不清楚。在这里，我们表明，一部分 AChR 抗体阴性的患者具有针对 Lrp4 的自身抗体。这些抗体抑制 Lrp4 与其配体的结合，并且主要属于免疫球蛋白 G1（IgG1）亚类，是补体激活物。这些发现共同表明 Lrp4 抗体参与了 AChR 抗体阴性 MG 的发病机制。
