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Common Pathways of Autoimmune Inflammatory Myopathies and Genetic Neuromuscular Disorders

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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.

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Authors and Affiliations

  1. Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, P.O. Box 100221, Gainesville, FL, 32610-0221, USA

    Minoru Satoh

  2. Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, 32610-0424, USA

    Minoru Satoh

  3. Department of Oral Biology, University of Florida, Gainesville, FL, 32610-0424, USA

    Angela Ceribelli & Edward K. L. Chan

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  1. Minoru Satoh
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  2. Angela Ceribelli
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  3. Edward K. L. Chan
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Correspondence to Minoru Satoh.

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This study is supported in part by a grant from the Lupus Research Institute and the National Institutes of Health grant AI47859.

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Satoh, M., Ceribelli, A. & Chan, E.K.L. Common Pathways of Autoimmune Inflammatory Myopathies and Genetic Neuromuscular Disorders. Clinic Rev Allerg Immunol 42, 16–25 (2012). https://doi.org/10.1007/s12016-011-8286-7

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