Objective:

To determine the risk of false acetylcholine receptor (AChR)-IgG positivity by radioimmune precipitation assay (RIPA), and investigate its determinants.

Background:

RIPA is the gold standard for AChR-IgG detection in patients with suspected myasthenia gravis (MG), with a reported specificity of ≈99%. The reported risk of false AChR-IgG positivity is extremely low, although the accuracy of RIPA in large, unselected populations has not been elucidated.

Design/Methods:

Among 4795 patients consecutively tested for AChR-IgG by RIPA at the University Hospital of Sassari between January 2003-March 2022, we retrospectively identified those with: 1) AChR-IgG positivity (titer ≥0.5 nmol/L); and 2) sufficient clinical information. Medical records were reviewed by two investigators and AChR-IgG was considered falsely positive when: 1) clinical-phenotypes were not consistent with MG; and/or 2) an alternative diagnosis was identified. Specificity and positive predictive value (PPV) were calculated, and the characteristics of patients with false vs true AChR-IgG positivity compared.

Results:

Of 362 AChR-IgG-positive patients included in the study, 50 (13.8%) were designated as false positives. Specificity and PPV were 98.9% (95% CI, 98.5-99.2) and 86.2% (95% CI, 82.2-89.6), respectively. Alternative diagnoses included ocular diseases (n=8), rheumatic diseases (n=7), pseudoptosis (n=5), myopathy (n=4), isolated cranial nerve palsy (n=2), parkinsonism (n=2), demyelinating diseases (n=2), and others (n=20). Compared to patients with MG, patients with false AChR-IgG were younger (median age, 65 [range, 7-91] vs 38 [range, 5-80] years), more frequently female (155/312 [49.8%] vs 37/50 [74%]), and had lower antibody titers (median, 6 [range, 0.5-28] vs 0.7 [range, 0.5-5.5] nmol/L). After stratification by titer ≥1 nmol/L, specificity and PPV increased to 99.8% (95% CI, 99.6-99.9) and 96.6% (95% CI, 94-98.3), respectively.

Conclusions: