title: Common pathways of autoimmune inflammatory myopathies and genetic neuromuscular disorders.
abstract: It has been shown that many hereditary motor neuron diseases are caused by mutation of RNA processing enzymes. Survival of motor neuron 1 (SMN1) is well-known as a causative gene for spinal muscular atrophy (SMA) and mutations of glycyl- and tyrosyl-tRNA synthetases are identified as a cause of distal SMA and Charcot-Marie-Tooth disease. Why and how the dysfunction of these ubiquitously expressed genes involved in RNA processing can cause a specific neurological disorder is not well understood. Interestingly, SMN complex has been identified recently as a new target of autoantibodies in polymyositis (PM). Autoantibodies in systemic rheumatic diseases are clinically useful biomarkers associated with a particular diagnosis, subset of a disease, or certain clinical characteristics. Many autoantibodies produced in patients with polymyositis/dermatomyositis (PM/DM) target RNA-protein complexes such as aminoacyl tRNA synthetases. It is interesting to note these same RNA-protein complexes recognized by autoantibodies in PM/DM are also responsible for genetic neuromuscular disease. Certain RNA-protein complexes are also targets of autoantibodies in paraneoplastic neurological disorders. Thus, there are several interesting associations between RNA-processing enzymes and neuromuscular disorders. Although pathogenetic roles of autoantibodies to intracellular antigens are generally considered unlikely, understanding the mechanisms of antigen selection in a particular disease and specific neurological symptoms caused by disruption of ubiquitous RNA-processing enzyme may help identify a common path in genetic neuromuscular disorders and autoimmunity in inflammatory myopathies.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610-0221, USA. minoru.satoh@medicine.ufl.edu
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Angela
authors.initials: A
authors.lastname: Ceribelli
authors.forename: Edward K L
authors.initials: EK
authors.lastname: Chan
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology*; D003882:Dermatomyositis / Q000235:genetics / Q000276:immunology; D006801:Humans; D009220:Myositis / Q000235:genetics* / Q000276:immunology*; D009468:Neuromuscular Diseases / Q000235:genetics* / Q000276:immunology*; D012313:RNA / Q000235:genetics / Q000276:immunology
chemical_list: D001323:Autoantibodies; D012313:RNA
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