Background and Objectives Radioimmunoprecipitation assay (RIPA) is the gold standard for acetylcholine receptor (AChR)–immunoglobulin G (IgG) detection in patients with myasthenia gravis (MG), with a reported specificity of ≈99%. The risk of “false” AChR-IgG positivity in clinical practice is often considered negligible, although data on large, real-life populations are scarce. The objective of this study was to determine the positive predictive value (PPV) and risk of false AChR-IgG positivity with RIPA in a large cohort of patients with suspected MG. Methods We retrospectively identified patients consecutively tested for AChR-IgG by RIPA at the University-Hospital of Sassari over 20 years (2003–2022) (n = 4,795). Medical records of AChR-IgG–positive patients (titer ≥0.5 nmol/L) were reviewed by 2 investigators to identify nonmyasthenic cases with false antibody positivity, defined as follows: (1) clinical phenotypes not consistent with MG and/or (2) symptoms better explained by alternative diagnoses. The characteristics of myasthenic and nonmyasthenic patients with AChR-IgG positivity were compared. A sample of nonmyasthenic patients was retested by fixed cell-based assay (CBA). Results Among 445 of 4,795 patients testing positive for AChR-IgG during the study period, 83 were excluded (insufficient information). Of 362 AChR-IgG–positive patients included, 50 (13.8%) were designated as nonmyasthenic. The PPV and specificity were 86.2% (95% CI 82.2–89.6) and 98.9% (95% CI 98.5–99.2), respectively. Alternative diagnoses in nonmyasthenic patients included ophthalmologic diseases (n = 8), rheumatic diseases (n = 7), pseudoptosis (n = 5), myopathy (n = 4), functional disorders (n = 3), cranial nerve palsy (n = 2), parkinsonism (n = 2), demyelinating diseases (n = 2), and others (n = 17). Compared with patients with MG, nonmyasthenic patients 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%]), had lower AChR-IgG titers (median 6 [range 0.5–28] vs 0.7 [range 0.5–5.5] nmol/L), and were more likely to become seronegative on subsequent tests (9/120 [8%] vs 6/11 [55%]). After stratification by titer ≥1 nmol/L, the PPV increased to 96.6% (95% CI 94–98.3). Serum of 7 nonmyasthenic patients was retested by CBA, giving negative results (n = 6) or selective positivity against the fetal AChR isoform (n = 1). Discussion False AChR-IgG positivity may occur in clinical practice with RIPA and associates with low antibody titer. Caution is needed when titers between 0.5 and 0.9 nmol/L are detected in low-probability situations because failure to recognize false antibody positivity may lead to misdiagnosis and inappropriate treatments.
Risk of False Acetylcholine Receptor Autoantibody Positivity by Radioimmunoprecipitation Assay in Clinical Practice
Puci, Mariangela;
2025-01-01
Abstract
Background and Objectives Radioimmunoprecipitation assay (RIPA) is the gold standard for acetylcholine receptor (AChR)–immunoglobulin G (IgG) detection in patients with myasthenia gravis (MG), with a reported specificity of ≈99%. The risk of “false” AChR-IgG positivity in clinical practice is often considered negligible, although data on large, real-life populations are scarce. The objective of this study was to determine the positive predictive value (PPV) and risk of false AChR-IgG positivity with RIPA in a large cohort of patients with suspected MG. Methods We retrospectively identified patients consecutively tested for AChR-IgG by RIPA at the University-Hospital of Sassari over 20 years (2003–2022) (n = 4,795). Medical records of AChR-IgG–positive patients (titer ≥0.5 nmol/L) were reviewed by 2 investigators to identify nonmyasthenic cases with false antibody positivity, defined as follows: (1) clinical phenotypes not consistent with MG and/or (2) symptoms better explained by alternative diagnoses. The characteristics of myasthenic and nonmyasthenic patients with AChR-IgG positivity were compared. A sample of nonmyasthenic patients was retested by fixed cell-based assay (CBA). Results Among 445 of 4,795 patients testing positive for AChR-IgG during the study period, 83 were excluded (insufficient information). Of 362 AChR-IgG–positive patients included, 50 (13.8%) were designated as nonmyasthenic. The PPV and specificity were 86.2% (95% CI 82.2–89.6) and 98.9% (95% CI 98.5–99.2), respectively. Alternative diagnoses in nonmyasthenic patients included ophthalmologic diseases (n = 8), rheumatic diseases (n = 7), pseudoptosis (n = 5), myopathy (n = 4), functional disorders (n = 3), cranial nerve palsy (n = 2), parkinsonism (n = 2), demyelinating diseases (n = 2), and others (n = 17). Compared with patients with MG, nonmyasthenic patients 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%]), had lower AChR-IgG titers (median 6 [range 0.5–28] vs 0.7 [range 0.5–5.5] nmol/L), and were more likely to become seronegative on subsequent tests (9/120 [8%] vs 6/11 [55%]). After stratification by titer ≥1 nmol/L, the PPV increased to 96.6% (95% CI 94–98.3). Serum of 7 nonmyasthenic patients was retested by CBA, giving negative results (n = 6) or selective positivity against the fetal AChR isoform (n = 1). Discussion False AChR-IgG positivity may occur in clinical practice with RIPA and associates with low antibody titer. Caution is needed when titers between 0.5 and 0.9 nmol/L are detected in low-probability situations because failure to recognize false antibody positivity may lead to misdiagnosis and inappropriate treatments.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
