Live cell-based assay (CBA) can aid in the diagnosis of myasthenia gravis (MG) in patients with seronegative MG through radioimmunoassay (RIA), according to a recently published article in Neurology Neuroimmunology and Neuroinflammation.

Although RIA is currently the gold standard for the detection of acetylcholine receptor (AChRs) and muscle-specific tyrosine kinase (MuSK) antibodies in patients with a clinical background suggestive of MG, approximately 15% of patients do not have detectable antibodies through RIA and are often diagnosed with double seronegative MG, the researchers noted.

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According to recent studies, live CBA is superior to RIA in the serologic diagnosis of MG; however, it is currently limited to specialized laboratories, mainly due to the required level of expertise. 

The recently available commercial fixed CBA has proven to be more sensitive than RIA, but there are no studies comparing it to live CBA, the study team noted.

“The aims of this study were to (1) compare the performance of fixed and live CBAs in the detection of AChR and MuSK Abs in patients with RIA-double seronegative MG and (2) assess their sensitivity in RIA-positive samples and their specificity in healthy and neurologic disease controls,” the authors wrote. 

The retrospective study included close to 300 samples, of which approximately 200 were from patients with confirmed MG and the rest from healthy controls and patients with other neurological disorders like multiple sclerosis. RIA was performed with commercial assays in all cases. Results from live and fixed CBA were compared using the McNemar test.

Of the samples included in the study, 86 were double seronegative through RIA. Double seronegative patients had a median age of 34, approximately 50% had only ocular involvement, and lonely 3 had a concomitant autoimmune disorder. 

Results showed that both fixed and live CBA were superior to RIA, with the former detecting MG antibodies in 10 of 86 patients with RIA double seronegative MG and the latter in 16 of 86 samples, representing an 8% increase rate of live CBA compared to fixed CBA. The authors noted that all positive samples by fixed CBA were also positive with live CBA. Notably, no patient double positive for AChR and MuSK antibodies.

Among RIA seropositive patients, fixed CBA had a sensitivity of 98.5% compared to a 100% observed with CBA. The specificity of both tests was 100%.

“In summary, we confirmed that fixed CBA has an increased capability to detect AChR and MuSK Abs compared with RIA and can therefore be useful in the serologic evaluation of patients with RIA-dSN MG or as a first-step diagnostic test,” the authors concluded. 


Spagni G, Gastaldi M, Businaro P, et al. Comparison of fixed and live cell-based assay for the detection of ACHR and musk antibodies in myasthenia gravis. Neurol Neuroimmunol Neuroinflamm. Published January 1, 2023. doi:10.1212/nxi.0000000000200038