An Algorithm for Acetylcholine Receptor Antibody Testing in Patients with Suspected Myasthenia Gravis

Haven, Thomas R.; Astill, Mark E.; Pasi, Brian M.; Carper, James B.; Wu, Lily; Tebo, Anne E.; Hill, Harry R.

doi:10.1373/clinchem.2009.140392

Cited by 10 publications

(9 citation statements)

References 4 publications

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“…8 Improved specificity in MG diagnosis is especially relevant in the current environment where MG as well as other paraneoplastic tests are frequently being used for screening rather than confirmatory tools, a so-called "indication creep." 21,22,26 In our entire tested cohort, approximately 30% had a positive AChR-Bi or AChR-Mo test, which is higher than previous MG reports. 22 Therefore, we predict in cohorts with lower pretest probability of MG, more false-positives can be eliminated by this reflexing strategy.…”

Section: Discussioncontrasting

confidence: 59%

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Improving accuracy of myasthenia gravis autoantibody testing by reflex algorithm

Shelly

Paul

et al. 2020

Neurology

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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.

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Section: Discussioncontrasting

confidence: 59%

“…21 One large study of MG serologic tests has suggested that physicians are now ordering MG serologic tests for screening over confirmatory purpose. 22 In that study, 39,380 were tested but only 12% had a positive AChR-Bi or AChR-Mo result. The study could not inform on clinical accuracy as no patient information was available.…”

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confidence: 87%

Improving accuracy of myasthenia gravis autoantibody testing by reflex algorithm

Shelly

Paul

et al. 2020

Neurology

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“…In these assays, radiolabeled antigen is mixed with serum from patients (in the presence or absence of unlabeled antigen), the antibodies are captured on protein A or protein G coated beads, and the radioactivity in the sample is measured. Such fluid‐phase assays are used, for example, to detect binding or blocking autoantibodies in myasthenia gravis, using 125 I‐α‐bungarotoxin–labeled acetylcholine receptor (AChR) as the antigen …”

Section: Considerations In Choosing Detection Methods For Autoantibodiesmentioning

confidence: 99%

“…Such fluidphase assays are used, for example, to detect binding or blocking autoantibodies in myasthenia gravis, using 125 I-a-bungarotoxin-labeled acetylcholine receptor (AChR) as the antigen. 81 Immunohistochemistry has long been used to identify autoantibodies that can bind to nervous system tissue, and can be a very sensitive method to detect such antibodies. However, in most cases, human tissue is not used in these assays, and the tissue is often fixed.…”

Section: Considerations In Choosing Detection Methods For Autoantibodiesmentioning

confidence: 99%

Autoantibodies and their potential roles in diseases of the nervous system

Beasley

Greer

2015

Clinical & Exp Neuroim

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Autoantibodies are found in many disorders of the nervous system, including diseases affecting the peripheral nervous system (e.g. Guillain-Barr e syndrome and other peripheral neuropathies), the central nervous system (e.g. neuromyelitis optica, multiple sclerosis and limbic encephalitis) and the neuromuscular junction (e.g. myasthenia gravis), as well as in neuropsychiatric disorders and in paraneoplastic syndromes. Some of these antibodies are likely to play an important pathogenic role in disease development, whereas others might be useful biomarkers for disease. In the present review, the features of an autoantibody that enable it to be pathogenic (e.g. the antibody isotype and the target antigen against which the antibody is directed) and some of the different mechanisms by which pathogenic autoantibodies could act will be discussed. These mechanisms include antibody-mediated cell lysis, opsonization of target proteins for attack by macrophages, crosslinking of Fc receptors, blocking or destroying receptors involved in neurotransmission or cellular homeostasis, and blocking of repair mechanisms such as remyelination. Examples will be given of diseases where these antibody-mediated mechanisms are known or thought to be active. Finally, approaches to treating autoantibody-mediated disease in the nervous system will be briefly reviewed.

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“…Over 85% of AChR antibody-positive MG blood samples exhibit AChR binding antibodies, and this remains the most useful clinical laboratory test. 26 Anti-MuSK positivity has been reported to account for one-third to one-half of AChR-antibody-negative MG cases, all exhibiting generalized weakness, and may be tested for separately. 27 However, further laboratory testing of seronegative patients is often not necessary in cases where the diagnosis has been established by additional ancillary testing.…”

Section: Serologic Testingmentioning

confidence: 99%

Pediatric Myasthenia Gravis: A Review

Berezovsky

Sitko

2016

J Pediatr Neurol

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Myasthenia gravis refers to a group of diseases affecting the neuromuscular junction resulting in muscle weakness. The clinical hallmark of this condition is skeletal muscle weakness that worsens with sustained or repetitive muscle activation, caused via disruption of neuromuscular transmission by antibodies directed most commonly against the nicotinic acetylcholine receptor. Transient neonatal myasthenia gravis is caused by the crossing of antibodies from a myasthenic mother to her developing child, while juvenile myasthenia gravis involves the production of antibodies by the child's own immune system against neuromuscular junction components. Ptosis and extraocular muscle weakness are common presenting symptoms of juvenile myasthenia gravis and may be accompanied by, or progress to, generalized weakness. Diagnosis of myasthenia gravis relies on careful neurological examination, supported by additional diagnostic modalities which may include the patient's response to short-acting cholinesterase inhibitors, serum testing for causative antibodies, or electromyography. Management options include cholinesterase inhibitors for symptomatic treatment, immunosuppression with corticosteroids or steroid-sparing immunosuppressants, and thymectomy when a thymoma is identified on imaging.

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An Algorithm for Acetylcholine Receptor Antibody Testing in Patients with Suspected Myasthenia Gravis

Cited by 10 publications

References 4 publications

Improving accuracy of myasthenia gravis autoantibody testing by reflex algorithm

Improving accuracy of myasthenia gravis autoantibody testing by reflex algorithm

Autoantibodies and their potential roles in diseases of the nervous system

Pediatric Myasthenia Gravis: A Review

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