[pubmed] Improving accuracy of myasthenia gravis autoantibody testing by reflex algorithm

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Neurology. 2020 Sep 16:10.1212/WNL.0000000000010910. doi: 10.1212/WNL.0000000000010910. Online ahead of print.

ABSTRACT

OBJECTIVE: To improve myasthenia gravis (MG) autoantibody testing.

METHODS: MG serological tests with confirmatory or refuting clinical-electrodiagnostic (EDX) testing and cancer evaluations were reviewed over 4-years (2012-2015). All patients had acetylcholine-receptor-binding (AChR-Bi), modulating (AChR-Mo) and striational (STR) autoantibody testing, and negatives reflexed to muscle-specific-kinase (MuSK). Thymoma and cancer occurrences were correlated with STR and reflexed glutamic-acid-decarboxylase-65 (GAD65), ganglionic-acetylcholine-receptor (alpha-3), collapsin-response-mediating-protein-5 (CRMP5), and voltage-gated-potassium-channel-complex (VGKC) autoantibodies.

RESULTS: Of 433 tested, 133 (31%) met clinical-EDX criteria for MG. Best sensitivity (90%) occurred at AChR-Bi>0.02nmol/L, leaving 14 negative (6-ocular-MG, 7-generalized-MG, 1-MuSK-MG) with specificity 90% (31 false-positives). Using AChR-Mo antibodies (>20% loss) specificity was better (92%, 24 false-positives), however sensitivity dropped (85%). Specificity improved (95%) by testing AChR-Mo when AChR-Bi are positives, resulting in 45% reduction of false-positives (31 to 17), maintaining AChR-Bi 90% sensitivity. Cut-off values recommended by area-under-curve analysis did not outperform this approach. AChR-Bi and AChR-Mo values were significantly higher in true-positives. Computed tomography (CT) evaluations in 121 MG revealed 16 thymomas. Historical or subsequent cancers occurred in 22. STR and reflexed autoantibodies were not more common in MG with thymoma or other cancers. Full-body CT (n=34) was performed in those with STR and reflex autoantibody positivity, but without additional cancers found.

CONCLUSION: Accuracy of MG serological testing is improved by reflexing AChR-Bi positive cases to AChR-Mo. STR and other reflexed cancer evaluation autoantibodies did not provide value beyond standard CT-chest imaging at the time of MG diagnosis. Diagnostic certainty is informed by AChR-Bi and AChR-Mo with higher values increasing specificity.

PMID:32938782 | DOI:10.1212/WNL.0000000000010910


Source: https://pubmed.ncbi.nlm.nih.gov/3293878 ... 2&v=2.11.5