4 Of these, 85% have hyperplasia (germinal-center formation) and 15% have thymomas. Moreover, approximately 75% of patients display thymic abnormalities. 2, 3 Because the thymus is a key organ in the production and education of functional T lymphocytes, it may be implicated in the initiation and progress of MG. 1 Although the production of anti-AChR antibodies is directly attributable to B cells, extensive evidence indicates that T cells have a key role in the autoantibody response. Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies against the nicotinic acetylcholine receptor (nAChR) on the postsynaptic membrane at the neuromuscular junction (NMJ) and characterized by weakness and fatigability of the voluntary muscles. Together, these findings show that modified AChE gene expression and properties are causally involved in thymic function and development. We further analyzed microarray data of MG thymic hyperplasia compared with healthy controls and found continuous and discrete changes in AChE-annotated GO categories. Interestingly, AChE-R transgenic mice showed increased numbers of CD4 +CD8 + cells that were considerably more resistant in vitro to apoptosis than normal thymocytes, suggesting possibly altered positive selection. To explore possible causal association of AChE-R changes with thymic composition and function, we used an AChE-R transgenic model and showed smaller thymic medulla compared with strain-matched controls, indicating that AChE-R overexpression interferes with thymic differentiation mechanisms. We found lower hydrolytic activities in the MG thymus compared with adult controls, accompanied by translocation of AChE-R from the cytoplasm to the membrane and increased expression of the signaling protein kinase PKC-βII. The objectives of this study were to analyze the involvement of AChE variants in thymic hyperplasia. MG is associated with thymic hyperplasia, showing signs of inflammation. Autoimmune myasthenia gravis (MG) is mediated by antibodies to the acetylcholine receptor and current therapy is based on anti-AChE drugs.
Cholinergic signaling and acetylcholinesterase (AChE) influence immune response and inflammation.
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