Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies that target the neuromuscular junction, leading to muscle weakness and fatigability. Currently available treatments for the disease include symptomatic pharmacological treatment, immunomodulatory drugs, plasma exchange, thymectomy and supportive therapies. Different autoantibody patterns and clinical manifestations characterize different subgroups of the disease: early-onset MG, late-onset MG, thymoma MG, muscle-specific kinase MG, low-density lipoprotein receptor-related protein 4 MG, seronegative MG, and ocular MG. These subtypes differ in terms of clinical characteristics, disease pathogenesis, prognosis and response to therapies. Patients would, therefore, benefit from treatment that is tailored to their disease subgroup, as well as other possible disease biomarkers, such as antibodies against cytoplasmic muscle proteins. Here, we discuss the different MG subtypes, the sensitivity and specificity of the various antibodies involved in MG for distinguishing between these subtypes, and the value of antibody assays in guiding optimal therapy. An understanding of these elements should be useful in determining how to adapt existing therapies to the requirements of each patient.
Key points
- The characteristic muscle weakness in myasthenia gravis (MG) is caused by antibodies directed against the neuromuscular junction
- MG is divided into subgroups on the basis of specific antibodies, other biomarkers, and clinical characteristics, such as age of onset, presence of thymoma, and involvement of ocular muscles
- The most common antibodies detected in MG are antibodies against acetylcholine receptors (AChRs), muscle-specific kinase (MuSK) and low-density lipoprotein receptor-related protein 4 (LRP4)
- Additional antibodies of interest in MG are directed against agrin, titin, KV1.4, ryanodine receptors, collagen Q, and cortactin
- Therapy should be tailored to the individual patient and guided by MG subgroup, and can include symptomatic drug therapy, immunosuppressive drug therapy, thymectomy and/or supportive therapy
- The aim of treatment should be normal or near-normal function, which in most patients requires long-term immunosuppressive treatment with a drug combination that is individualized for the patient for optimal effectiveness
Introduction
Myasthenia gravis (MG) is an autoimmune disorder caused by antibodies targeting the neuromuscular junction. In MG, these antibodies bind to the postsynaptic muscle end-plate and attack and destroy postsynaptic molecules. This process leads to impaired signal transduction and, consequently, muscle weakness and fatigability — the hallmark symptoms of MG. The weakness can be focal or generalized, and usually affects ocular, bulbar and proximal extremity muscles. Respiratory muscle weakness develops only rarely, but can be life-threatening. Weakness is typically symmetrical, except in affected external eye muscles, in which the weakness is usually asymmetrical.
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| Neuromuscular junction in myasthenia gravis (MG) |
Source: NatureReviewsNeurolog
