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Science News: Clinical Value of Cell-Based Assays in the Characterisation of Seronegative Myasthenia Gravis

1/19/2023
 
Submitted by: Pritikanta Paul, MD
Edited by: Nakul Katyal, MD


Damato V, Spagni G, Monte G, et al. Clinical value of cell-based assays in the characterisation of seronegative myasthenia gravis. J Neurol Neurosurg Psychiatry. 2022;93(9):995-1000. doi:10.1136/jnnp-2022-329284

Summary: Although autoantibody testing is critical for the diagnosis of myasthenia gravis (MG) in current clinical practice, the test can be negative in up to 10% of cases of generalized MG and up to 50% of cases of ocular MG. These seronegative patients often have delayed diagnosis and potentially can have an erroneous diagnosis. A cell-based assay (CBA) can improve the diagnostic yield of the antibody testing when compared to standardized commercially available radioimmunoassay (RIA) but it is mostly restricted to research institutions. This study retrospectively looked at consecutive MG patients in a single tertiary referral center to assess the clinical significance of CBA approach and compared with cases positive for AChR and MuSK tested by RIA.
 
Stored sera of 82 patients with diagnosis of seronegative MG (SNMG) were tested by live-CBA. Nearly one-third (N=23) tested positive for either AChR or MuSK antibodies, but none tested positive for LRP4. CBA- positive AChR patients were majority early-onset (<50 yrs age), frequently ocular, and most had mild disease course when compared with RIA-positive AChR patients. CBA- positive MuSK antibodies had milder disease course than RIA-positive MuSK cases. Patients who received early immunotherapy achieved a better outcome than those in whom immunotherapy was delayed.
 
Some of the major limitations of the study include retrospective nature, testing of samples of patients while on immunotherapy, as well as limited data on the genetic testing for the seronegative patients. However, this study highlights the importance of including CBAs in diagnostic workup for MG.

Comments: While use of live-CBAs is currently restricted to research settings currently, given the requirement of expertise and cell-culture facilities, a fixed-CBA could be a reasonable alternative based on a recent study. Further well designed studies are required to explore the diagnostic utility and feasibility of CBA in MG diagnosis without use of radiolabeled ligands.

Article of Similar Interest: 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. 2022;10(1):e200038. Published 2022 Oct 21. doi:10.1212/NXI.0000000000200038
 


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