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Reference range review for the RSR acetylcholine receptor antibody assay

Establishing optimal cut-off values is essential in ensuring excellent results accuracy and quality, a prime example being in facilitating the diagnosis of myasthenia gravis and its appropriate treatment. Here, Rebecca Cottage and colleagues from Manchester report on measures undertaken to check and amend the reference range for anti-acetylcholine receptor antibodies.

Myasthenia gravis (MG) is the most common autoimmune condition to affect the neuromuscular junction, and is characterised by progressive skeletal muscle weakness and fatiguability. Detection of anti-acetylcholine receptor (AChR) antibodies is frequently used as a first-line investigation for MG. The authors’ laboratory currently uses the RSR enzyme-linked immunosorbent assay (ELISA) kit for this test, with a quoted manufacturer’s cut-off value of 0.45 nmol/L. 

Initial verification of the assay with healthy blood donor sera indicated that the manufacturer’s cut-off value may be too low, with further observations from routine testing showing a high incidence of low-positive results. These findings plus a recent UK NEQAS non-conformity has prompted a review and revision of the established cut-off. 

Anti-AChR values were obtained from a cohort of 29 neurology and 11 ophthalmology patients with established MG. Here, the authors describe the use of Receiver Operator Curve (ROC) analysis to establish a new optimal cut-off value for the assay. As detailed in this article, preliminary analysis implies that the specificity is much improved, the new cut-off is more clinically relevant, in line with published data, and should not lead to further external quality assessment (EQA) misclassifications.

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