Andy
Senior Member (Voting rights)
Full title: Myasthenia gravis with antibodies against the AChR, current knowledge on pathophysiology and an update on treatment strategies with special focus on targeting plasma cells
Highlights
• Thymic involution, follicular hyperplasia and thymoma observed in AChR-MG are associated with tolerance disruption.
• Autoantibody levels could serve as a good individualized predictive tool for therapeutic response.
• Formation of autoreactive T and antibody producing cells in the thymus and their migration to the periphery could be the cause of lack of efficacy of thymectomy.
• Antibody-producing cells targeting therapies are needed for patients not responding to classical immunotherapy.
Abstract
Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder where the neuromuscular transmission is impaired, causing symptoms of skeletal muscle weakness and fatigue. The presence of autoantibodies against the muscle nicotinic acetylcholine receptor (AChR) is the most prevalent cause of MG. Abnormalities in the thymus are common in AChR-MG, and thymectomy has proven to be therapeutically beneficial. Up to 30 % of AChR-MG patients have also thymoma. Moreover, patients with thymoma without MG are more prompt to develop MG compared to the general population.
Autoantibodies in AChR-MG damage the postsynaptic membrane of the neuromuscular junction (NMJ) and cause muscle weakness by impairing synaptic transmission because of the depletion of the AChRs and destruction of the NMJ. The pathogenic autoantibody levels vary greatly between patients. In contrast, in individual patients changes in autoantibody levels correlate well with disease severity.
A small selection of patients has been used to exemplify the individual relationship between autoantibody levels and disease progression. The study of the effector functions of the autoantibodies and the compensatory mechanisms at the NMJ are important to select the best treatment strategy for each patient. Even though classical immunomodulatory treatments are effective in many patients, around 10–20 % of patients do not respond to current therapies. This may be attributed to the production of autoantibodies by different circulating cells including mature B and long-lived plasma cells, which are resistant to most commonly used immunosuppressive drugs. Hence, novel therapies specifically targeting plasma cells might be a suitable therapeutic approach for selected refractory patients.
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Highlights
• Thymic involution, follicular hyperplasia and thymoma observed in AChR-MG are associated with tolerance disruption.
• Autoantibody levels could serve as a good individualized predictive tool for therapeutic response.
• Formation of autoreactive T and antibody producing cells in the thymus and their migration to the periphery could be the cause of lack of efficacy of thymectomy.
• Antibody-producing cells targeting therapies are needed for patients not responding to classical immunotherapy.
Abstract
Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder where the neuromuscular transmission is impaired, causing symptoms of skeletal muscle weakness and fatigue. The presence of autoantibodies against the muscle nicotinic acetylcholine receptor (AChR) is the most prevalent cause of MG. Abnormalities in the thymus are common in AChR-MG, and thymectomy has proven to be therapeutically beneficial. Up to 30 % of AChR-MG patients have also thymoma. Moreover, patients with thymoma without MG are more prompt to develop MG compared to the general population.
Autoantibodies in AChR-MG damage the postsynaptic membrane of the neuromuscular junction (NMJ) and cause muscle weakness by impairing synaptic transmission because of the depletion of the AChRs and destruction of the NMJ. The pathogenic autoantibody levels vary greatly between patients. In contrast, in individual patients changes in autoantibody levels correlate well with disease severity.
A small selection of patients has been used to exemplify the individual relationship between autoantibody levels and disease progression. The study of the effector functions of the autoantibodies and the compensatory mechanisms at the NMJ are important to select the best treatment strategy for each patient. Even though classical immunomodulatory treatments are effective in many patients, around 10–20 % of patients do not respond to current therapies. This may be attributed to the production of autoantibodies by different circulating cells including mature B and long-lived plasma cells, which are resistant to most commonly used immunosuppressive drugs. Hence, novel therapies specifically targeting plasma cells might be a suitable therapeutic approach for selected refractory patients.
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