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, 69 (2), 418-22

Autoantibodies to Low-Density Lipoprotein Receptor-Related Protein 4 in Myasthenia Gravis

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Autoantibodies to Low-Density Lipoprotein Receptor-Related Protein 4 in Myasthenia Gravis

Osamu Higuchi et al. Ann Neurol.

Abstract

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.

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