Common Pathways of Autoimmune Inflammatory Myopathies and Genetic Neuromuscular Disorders

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.