Subunit-specific autoantibodies in autoimmune autonomic ganglionopathy

Nicolás Urriola; Katrina Blazek; Stephen Adelstein

doi:10.1016/j.jneuroim.2021.577805

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.

Authors

Nicolás Urriola¹, Katrina Blazek², Stephen Adelstein³

Affiliations

¹ Department of Clinical Immunology and Allergy, Royal Prince Alfred Hospital, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: nicolas.urriola@health.nsw.gov.au.
² School of Population Health, UNSW, Sydney, New South Wales, Australia.
³ Department of Clinical Immunology and Allergy, Royal Prince Alfred Hospital, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Central Sydney Immunopathology Laboratory, Pathology East, NSW Health Pathology, Australia.

PMID: 34995917
DOI: 10.1016/j.jneuroim.2021.577805

Abstract

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

Substances

Autoantibodies
Autoantigens
Receptors, Cholinergic