What you need to know about antibodies in myasthenia gravis
Myasthenia Gravis is not a new disease. Only the antibodies are. In fact the first case of myasthenia gravis was described in the late 17th century. It would be over 250 years before any form of treatment was deemed effective, and even then, we lacked a precise understanding of the pathophysiology of this disease.
In this BrainWaves brief, not only do we take a tour through the history of this autoimmune, and occasionally paraneoplastic, condition. But we also review the various mechanisms by which autoantibodies can affect the neuromuscular junction:
As a medical student, you are taught that myasthenia gravis is the result of auto-antibodies that target the nicotinic acetylcholine receptor at the neuromuscular junction, or AchR-antibodies. As a matter of fact, it is far more complicated. According to the literature, about 80% of myasthenic patients have antibodies against the acetylcholine receptor, leaving approximately 20% “seronegative.” For patients without AchR-antibodies, other antibodies have been identified over the last few decades. Perhaps most recognized is the presynaptic calcium channel antibody, which results in the classic Lambert Eaton Myasthenic Syndrome–a disease pathophysiologically distinct from myasthenia gravis, and one associated with small cell lung cancer. In LEMS, the textbook tells us these patients lack the “fatigability” of classic myasthenia gravis. However, the concept of fatigability is more of an electromyographic concept, rather than a symptomatic one. Proximal muscle weakness is heralded as a feature of both MG and LEMS (80% of patients’ presenting symptoms), making it an insensitive measure to clinically differentiate these syndromes. Unlike MG, LEMS may also present with autonomic features (90%) and areflexia (40%).
Other antibodies in MG include those which target muscle specific kinase (anti-MuSK) and lipoprotein-related protein 4 (anti-LRP4), which together may account for 5-6% of all cases of MG. The syndromes may be clinically unique from that of AchR-antibody myasthenia, but often providers will proceed with AchR-antibody testing first before moving onto these other, rarer antibody types. To learn more from here, check out our latest podcast, and let us know what you think!
The content in this episode was vetted and approved by Grant T. Liu.
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