Abstract Details

Title Risk of “False Positivity” Associates with Acetylcholine Receptor Autoantibody Titer by Radioimmunoprecipitation Assay

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P8 - Poster Session 8 (8:00 AM-9:00 AM)

Poster/Presentation
Number 11-031

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

False AChR-IgG positivity by RIPA may occur in clinical practice, and associates with low antibody titers between 0.5-1 nmol/L. The risk of false positivity is negligible with higher AChR-IgG titers.

Authors/Disclosures
Pietro Zara, MD (University of Sassari) PRESENTER	Dr. Zara has nothing to disclose.
Paola Chessa, MD	Dr. Chessa has nothing to disclose.
Giovanni A. Deiana, Sr., PhD	Dr. Deiana has nothing to disclose.
Mariangela Puci, PhD	Dr. Puci has nothing to disclose.
Giovanni Sotgiu, MD, PhD	Prof. Sotgiu has nothing to disclose.
Valentina Damato, MD, PhD (Department of Neuroscience, University of Florence)	Dr. Damato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Damato has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Damato has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Pharma.
Paolo Solla, MD (Ospedale Binaghi)	Dr. Solla has nothing to disclose.
Elia Sechi, MD (University of Sassari)	Dr. Sechi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Sechi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenx.

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