Diagnostic Performance of Three Serological Assays in Myasthenia Gravis: A Prospective Multicentre Study.
Laura Cuomo, Laura De Giglio, Maria Antonietta Isgrò, Maria Totaro, Matteo Pratali, Caterina Fragomeli, Lorenzo Cosmi, Francesco Annunziato, Boaz Palterer, Maria Concetta Altavista, Giovanni Antonini, Marianna Brienza, Chiara Cambieri, Francesca Cortese, Laura Fionda
Abstract
Open AccessAnti-acetylcholine receptor (AChR) and anti-muscle-specific tyrosine kinase (MuSK) autoantibody detection is crucial in the diagnosis and choice of treatment of myasthenia gravis (MG). We conducted a multicentre prospective study comparing radioimmunoprecipitation assay (RIPA), enzyme-linked immunosorbent assay (ELISA) and fixed cell-based assay (F-CBA) for anti-AChR and anti-MuSK antibody detection in 78 patients with suspected MG with at least 6 months of clinical follow-up. In the diagnosis of seropositive MG (anti-AChR+anti-MuSK abs), RIPA was most sensitive (82.8%) compared to ELISA (81.0%) and F-CBA (70.7%). F-CBA exhibited the highest specificity overall (95.0%). For anti-AChR detection, F-CBA demonstrated a sensitivity of 73.6% and specificity of 95.0%; ELISA showed sensitivity and specificity of 81.1% and 85.0%, respectively; and RIPA yielded sensitivity and specificity of 81.1% and 95.0%. Sensitivity of F-CBA improved when sera were tested at lower dilution (1:5) versus the manufacturer's recommended 1:10, without compromising specificity. Agreement among methods was almost perfect for anti-AChR detection (Cohen's Kappa > 0.81). For anti-MuSK detection, agreement was substantial between ELISA and RIPA, moderate between ELISA and F-CBA, and fair between RIPA and F-CBA. Higher anti-AChR antibody levels were found in generalised versus ocular MG by both RIPA and ELISA. F-CBA confirmed its optimal specificity while the sensitivity seems to be influenced by sample dilution. In conclusion, given the radioactive nature of RIPA and consequent limitations, F-CBA may represent a valid alternative in anti-AChR and anti-MuSK antibody detection in MG diagnosis. We suggest that the use of live-CBA or RIPA could be reserved for inconclusive cases.