Journal
ANNALS OF NEUROLOGY
Volume 69, Issue 2, Pages 418-422Publisher
WILEY
DOI: 10.1002/ana.22312
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [20247024]
- Ministry of Health, Labour and Welfare of Japan [200936024A, 200936129A]
- Grants-in-Aid for Scientific Research [20247024] Funding Source: KAKEN
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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. ANN NEUROL 2011;69:418-422
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