Harnessing 40 years ofdiagnostic expertise to transformmyasthenia gravis detection.
Magali Wolff, Head of Global Reagent Marketing and Support, and Dr Constanze Drechsel, Product Manager, Tecan
June is myasthenia gravis (MG) awareness month, an important time to raise awareness about this complex, chronic neuromuscular disorder, which is estimated to affect more than 700,000 people worldwide.¹ MG is an autoimmune disease, in which the body’s own immune system produces antibodies that attack important proteins at neuromuscular junctions, affecting the skeletal muscles responsible for breathing and various other movements. Early and accurate diagnosis is important because, despite the absence of a cure, timely treatment can help to control symptoms and improve a patient’s quality of life. Fortunately, Tecan has 40 years of diagnostic expertise under its belt, and offers a range of biomarkers and targeted immunoassays to detect and quantify the autoantibodies linked to this condition, increasing the likelihood that MG patients are identified early and treated appropriately.
A complex condition
The hallmark of MG is muscle weakness – particularly in the muscles controlling the eyes and eyelids, facial expressions, chewing, swallowing and speaking – which worsens after periods of activity and improves with rest.² However, these symptoms overlap with many other disorders, and the degree of muscle weakness involved varies greatly from person to person, so diagnosis has historically often been missed or delayed.² Today, state-of-the-art disease biomarkers and targeted assays are available to help improve the speed and reliability of diagnosis.
In most cases of MG, autoantibodies target the acetylcholine receptors, transmembrane proteins that carry electrical signals between nerve endings and muscles to stimulate muscle contractions.³ Acetylcholine receptor autoantibodies (ARAbs) prevent acetylcholine from binding to its receptor, blocking normal muscle contractions. However, about 15 percent of patients with clinical symptoms will have no detectable ARAbs and, in these cases, the disease will be classed as seronegative.³ Approximately 40 percent of seronegative MG cases can be diagnosed based on the detection of autoantibodies to muscle-specific kinase (MuSK), a protein involved in cross-linking the acetylcholine receptor to the cytoskeleton.4 Seronegative patients tend to have a more severe form of the condition that demands more intensive therapy – with about 30 percent requiring respiratory support – making early and definitive diagnosis crucial.
Top product
MuSK-Ab ELISA from Tecan
- Field: Autoimmunity
- Sample type: Human serum
- Intended use: Enzyme immunoassay for the qualitative and quantitative determination of autoantibodies against muscle-specific receptor tyrosine kinase in human serum.
- Benefits: The MuSK-Ab ELISA is IVDR certified, and can be processed on open ELISA systems like the Freedom EVOlyzer®, DYNEX DSX® and GSD ThunderBolt®.**
Leading the way in MG diagnostics
Tecan’s expertise in MG diagnostics began in 1995, when the company pioneered a radioreceptor assay (RRA) to detect ARAbs. This assay uses receptors from human muscle in combination with a radio-labeled alpha-bungarotoxin snake venom marker that binds very specifically to acetylcholine receptors without interfering with ARAb binding. Not only is the RRA assay highly sensitive – making it the gold standard for serological diagnosis of MG – but it is also quantitative, which is particularly important with regards to the treatment of myasthenia gravis. Immunosuppressant therapies take time to work, and therapeutic monitoring based on measurements of ARAb-RRA can therefore be used to monitor ARAb levels, giving an early indication of remission or treatment failure.
In 2012, Tecan progressed its range of diagnostic tools of MG with the launch of an enzyme-linked immunosorbent assay (ELISA) to identify autoantibodies against muscle-specific tyrosine kinase (MuSK). This test is the world’s first commercially available, non-radioactive assay for detecting anti-MuSK autoantibodies, and is designed to help improve both diagnostic certainty and the clinical management and monitoring of seronegative MG patients. Due to the severity of this form of the disease, the therapy required – which usually involves rituximab immunosuppression to deplete B cells – is more intensive, and aims to completely eliminate anti-MuSK antibodies. A sensitive assay to monitor treatment outcomes is therefore vital, and Tecan’s anti-MuSK ELISA offers:
- Data integrity, with excellent clinical sensitivity (95.8 %) and specificity (100 %)
- Qualitative (cut-off) and quantitative (standard curve) evaluation of results
- A holistic diagnostic solution that can be processed on open ELISA systems**
Top product
ARAb RRA from Tecan
- Field: Autoimmunity
- Sample type: Human serum and EDTA plasma
- Intended use: Radio receptor assay for in vitro diagnostic, semi-quantitative determination of autoantibodies against the acetylcholine receptor in human serum and plasma.
- Benefits: Considered to be the gold standard for the supportive diagnosis of MG. The assay will be IVDR ready soon.*
At the forefront of innovation
Although there is no cure for MG, diagnosis and treatment of the condition has undergone considerable changes over the past 40 years. Tecan has played a key role in this progression, by developing a comprehensive solution for diagnosing both seropositive and seronegative MG patients. MG awareness month offers the perfect opportunity to highlight these groundbreaking detection solutions, while looking forward to future progress in MG research. Tecan continues to place a huge emphasis on developing novel solutions to ensure it stays at the forefront of modern diagnostics, and will be launching a new MG immunoassay to add to its current portfolio in the near future.
To find out more or to see our full portfolio please visit:
Disclaimers
* Product availability and regulatory status may vary across regions outside the EU, depending on local country-specific registration. CE IVD under IVDR in EU. Consult with your Tecan associate for further information.
** The combined use of the assay, process script and instrument must be validated individually on-site by each laboratory.
References
- Sanders, D.B. et al. International consensus guidance for management of Myasthenia Gravis. Neurology, 2016, 87(4), 419-425. doi: 10.1212/wnl.0000000000002790.
- Myasthenia Gravis. National Institute of Neurological Disorders and Stroke. Available at: https://www.ninds.nih.gov/health-information/disorders/myasthenia-gravis (Accessed: 19 May 2023).
- Lazaridis, K. and Tzartos, S.J. Myasthenia gravis: Autoantibody specificities and their role in MG Management. Frontiers in Neurology, 2020, 11. doi: 10.3389/fneur.2020.596981.
- Ali, H. et al. Muscle-specific tyrosine kinase-associated myasthenia gravis: A neuromuscular surprise. Case Reports in Neurological Medicine, 2021, 1-3. doi: 10.1155/2021/1326442.