Concordance between radioimmunoassay and fixed cell-based assay in subjects without myasthenia gravis: optimizing the diagnostic approach

Eur J Neurol. 2024 Dec;31(12):e16435. doi: 10.1111/ene.16435. Epub 2024 Aug 8.

Abstract

Background and purpose: Acetylcholine receptor antibody (AChR-Ab) detection is crucial in myasthenia gravis (MG) diagnosis and, currently, the radioimmunoassay (RIA) is the gold standard. However, RIA may detect AChR-Ab against nonpathogenic intracellular epitopes. In this study, we performed fixed cell-based assay (F-CBA) in RIA-AChR-Ab positive subjects without MG symptoms, to assess whether F-CBA could show a higher specificity compared to RIA in detecting pathogenic Abs.

Methods: We reviewed medical records of patients referred to our MG outpatient clinic because of RIA-AChR-Ab detection. MG diagnosis was based on clinical examination, electrophysiology and Ab detection. AChR-Abs were tested by RIA in the whole cohort. Serum samples from RIA-positive asymptomatic subjects were retested by F-CBA.

Results: Of 605 subjects who tested RIA-AChR-Ab positive, MG diagnosis was confirmed in 599. Six subjects were RIA-AChR-Ab positive although they had never had MG symptoms; in four of these subjects AChR-Abs were not detected by F-CBA, whereas the remaining two (both non-MG thymoma cases) were positive also by F-CBA.

Conclusions: RIA false positivity for AChR-Ab is very rare. Previous literature has demonstrated that F-CBA has higher sensitivity than RIA for MG, especially in ocular cases. Our preliminary results show that, in rare instances, F-CBA may be more specific than RIA for MG diagnosis.

Keywords: autoantibodies; autoimmune; diagnostic tests; nervous system; neuromuscular junction.

MeSH terms

  • Adult
  • Aged
  • Autoantibodies* / blood
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myasthenia Gravis* / blood
  • Myasthenia Gravis* / diagnosis
  • Myasthenia Gravis* / immunology
  • Radioimmunoassay* / methods
  • Radioimmunoassay* / standards
  • Receptors, Cholinergic* / immunology
  • Retrospective Studies
  • Sensitivity and Specificity

Substances

  • Receptors, Cholinergic
  • Autoantibodies