Myasthenia gravis seronegative for acetylcholine receptor antibodies in South Korea: Autoantibody profiles and clinical features

PLoS One. 2018 Mar 8;13(3):e0193723. doi: 10.1371/journal.pone.0193723. eCollection 2018.

Abstract

Acquired myasthenia gravis (MG) is a prototype autoimmune disease of the neuromuscular junction, caused in most patients by autoantibodies to the muscle nicotinic acetylcholine receptor (AChR). There seem to be ethnic and regional differences in the frequency and clinical features of MG seronegative for the AChR antibody. This study aimed to describe the autoantibody profiles and clinical features of Korean patients with generalized MG seronegative for the AChR antibody. A total of 62 patients with a high index of clinical suspicion of seronegative generalized MG were identified from 18 centers, and we examined their sera for antibodies to clustered AChR, muscle-specific tyrosine kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (LRP4) by cell-based assays (CBA) and to MuSK by radioimmunoprecipitation assay (RIPA). We also included 8 patients with ocular MG, 3 with Lambert-Eaton myasthenic syndrome, 5 with motor neuron disease, and 9 with other diagnoses as comparators for the serological testing. Antibodies were identified in 25/62 (40.3%) patients: 7 had antibodies to clustered AChR, 17 to MuSK, and 2 to LRP4. Three patients were double seropositive: 1 for MuSK and LRP4, and 2 for MuSK and clustered AChR. The patients with MuSK antibodies were mostly female (88.2%) and characterized by predominantly bulbar involvement (70%) and frequent myasthenic crises (58.3%). The patients with antibodies to clustered AChR, including 2 with ocular MG, tended to have a mild phenotype and good prognosis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • Cross-Sectional Studies
  • Female
  • Follow-Up Studies
  • Humans
  • LDL-Receptor Related Proteins / immunology
  • Lambert-Eaton Myasthenic Syndrome / blood
  • Lambert-Eaton Myasthenic Syndrome / immunology
  • Male
  • Middle Aged
  • Motor Neuron Disease / blood
  • Motor Neuron Disease / immunology
  • Myasthenia Gravis / blood*
  • Myasthenia Gravis / immunology*
  • Radioimmunoprecipitation Assay
  • Receptor Protein-Tyrosine Kinases / immunology
  • Receptors, Cholinergic / immunology*
  • Republic of Korea
  • Retrospective Studies

Substances

  • Autoantibodies
  • LDL-Receptor Related Proteins
  • LRP4 protein, human
  • Receptors, Cholinergic
  • MUSK protein, human
  • Receptor Protein-Tyrosine Kinases

Grants and funding

This work was supported by grants from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (800-20170353), the Seoul Metropolitan Government Seoul National University (SMG-SNU) Boramae Medical Center (03-2014-16). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.