Subunit-specific autoantibodies in autoimmune autonomic ganglionopathy

J Neuroimmunol. 2022 Feb 15:363:577805. doi: 10.1016/j.jneuroim.2021.577805. Epub 2022 Jan 2.


Autoimmune Autonomic Ganglionopathy (AAG) is a disorder that causes autonomic failure and is associated with alpha3-ganglionic acetylcholine-receptor (gnACHR) antibodies. Assays that detect antibodies to whole gnACHR or subunits are available. We compared in-house subunit-specific immunoassays using bacterially-expressed alpha3 and beta4 subunits against an immunomodulation assay to detect antibodies in patients with AAG or control groups in a novel 2-step clinical-characteristic unblinding protocol. Only 1/8 patients with seropositive-AAG had subunit-specific antibodies, with sensitivity, specificity, false-negative and positive rates of 12.5, 85.2, 78.6 and 13.4% respectively. Subunit-specific antibody-derived false-positive results can lead to misdiagnosis, as autonomic failure is not specific to AAG.

Keywords: Autoimmune autonomic ganglionopathy; Live-cell immunomodulation; Subunit-specific antibodies; alpha3; gnACHR.

MeSH terms

  • Autoantibodies / analysis*
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • Autoimmune Diseases of the Nervous System / diagnosis*
  • Autoimmune Diseases of the Nervous System / immunology
  • Autonomic Nervous System Diseases / diagnosis*
  • Autonomic Nervous System Diseases / immunology
  • Humans
  • Immunoassay / methods*
  • Receptors, Cholinergic / immunology
  • Sensitivity and Specificity


  • Autoantibodies
  • Autoantigens
  • Receptors, Cholinergic