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Statins and Myotoxic Effects Associated With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies: An Observational Study in Japan
Statins have a variety of myotoxic effects and can trigger the development of inflammatory myopathies or myasthenia gravis (MG) mediated by immunomodulatory properties. Autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) have been identified in patients with statin-associated m...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer Health
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602975/ https://www.ncbi.nlm.nih.gov/pubmed/25634171 http://dx.doi.org/10.1097/MD.0000000000000416 |
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author | Watanabe, Yurika Suzuki, Shigeaki Nishimura, Hiroaki Murata, Ken-ya Kurashige, Takashi Ikawa, Masamichi Asahi, Masaru Konishi, Hirofumi Mitsuma, Satsuki Kawabata, Satoshi Suzuki, Norihiro Nishino, Ichizo |
author_facet | Watanabe, Yurika Suzuki, Shigeaki Nishimura, Hiroaki Murata, Ken-ya Kurashige, Takashi Ikawa, Masamichi Asahi, Masaru Konishi, Hirofumi Mitsuma, Satsuki Kawabata, Satoshi Suzuki, Norihiro Nishino, Ichizo |
author_sort | Watanabe, Yurika |
collection | PubMed |
description | Statins have a variety of myotoxic effects and can trigger the development of inflammatory myopathies or myasthenia gravis (MG) mediated by immunomodulatory properties. Autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) have been identified in patients with statin-associated myopathy. The purpose of the present study is to develop an enzyme-linked immunosorbent assay (ELISA) of anti-HMGCR antibodies and to elucidate the clinical significance of anti-HMGCR antibodies in Japanese patients with inflammatory myopathies or MG. We enrolled 75 patients with inflammatory myopathies, who were all negative for anti-signal recognition particle and anti-aminoacyl transfer RNA synthetase antibodies. They were referred to Keio University and National Center of Neurology and Psychiatry between October 2010 and September 2012. We also studied 251 patients with MG who were followed at the MG Clinic at Keio University Hospital. Anti-HMGCR antibodies were detected by ELISA. We investigated demographic, clinical, radiological, and histological findings associated with anti-HMGCR antibodies. We established the anti-HMGCR ELISA with the recombinant protein. Protein immunoprecipitation detected autoantigens corresponding to HMGCR. Immunohistochemistry using muscle biopsy specimens revealed regenerating muscle fibers clearly stained by polyclonal anti-HMGCR antibodies and patients’ serum. Anti-HMGCR autoantibodies were specifically detected in 8 patients with necrotizing myopathy. The seropositivity rate in the necrotizing myopathy patients was significantly higher than those in the patients with other histological diagnoses of inflammatory myopathies (31% vs 2%, P = 0.001). Statins were administered in only 3 of the 8 anti-HMGCR-positive patients. Myopathy associated with anti-HMGCR antibodies showed mild limb weakness and favorable response to immunotherapy. All 8 patients exhibited increased signal intensities on short T1 inversion recovery of muscle MRI. Of the 251 patients with MG, 23 were administered statins at the onset of MG. One late-onset MG patient experienced MG worsening after 4-wk treatment with atorvastatin. However, anti-HMGCR antibodies were not detected in the 251 MG patients except for one early-onset MG patient with no history of statin therapy. Anti-HMGCR antibodies are a relevant clinical marker of necrotizing myopathy with or without statin exposure, but they are not associated with the onset or deterioration of MG. |
format | Online Article Text |
id | pubmed-4602975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Wolters Kluwer Health |
record_format | MEDLINE/PubMed |
spelling | pubmed-46029752015-10-27 Statins and Myotoxic Effects Associated With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies: An Observational Study in Japan Watanabe, Yurika Suzuki, Shigeaki Nishimura, Hiroaki Murata, Ken-ya Kurashige, Takashi Ikawa, Masamichi Asahi, Masaru Konishi, Hirofumi Mitsuma, Satsuki Kawabata, Satoshi Suzuki, Norihiro Nishino, Ichizo Medicine (Baltimore) 5300 Statins have a variety of myotoxic effects and can trigger the development of inflammatory myopathies or myasthenia gravis (MG) mediated by immunomodulatory properties. Autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) have been identified in patients with statin-associated myopathy. The purpose of the present study is to develop an enzyme-linked immunosorbent assay (ELISA) of anti-HMGCR antibodies and to elucidate the clinical significance of anti-HMGCR antibodies in Japanese patients with inflammatory myopathies or MG. We enrolled 75 patients with inflammatory myopathies, who were all negative for anti-signal recognition particle and anti-aminoacyl transfer RNA synthetase antibodies. They were referred to Keio University and National Center of Neurology and Psychiatry between October 2010 and September 2012. We also studied 251 patients with MG who were followed at the MG Clinic at Keio University Hospital. Anti-HMGCR antibodies were detected by ELISA. We investigated demographic, clinical, radiological, and histological findings associated with anti-HMGCR antibodies. We established the anti-HMGCR ELISA with the recombinant protein. Protein immunoprecipitation detected autoantigens corresponding to HMGCR. Immunohistochemistry using muscle biopsy specimens revealed regenerating muscle fibers clearly stained by polyclonal anti-HMGCR antibodies and patients’ serum. Anti-HMGCR autoantibodies were specifically detected in 8 patients with necrotizing myopathy. The seropositivity rate in the necrotizing myopathy patients was significantly higher than those in the patients with other histological diagnoses of inflammatory myopathies (31% vs 2%, P = 0.001). Statins were administered in only 3 of the 8 anti-HMGCR-positive patients. Myopathy associated with anti-HMGCR antibodies showed mild limb weakness and favorable response to immunotherapy. All 8 patients exhibited increased signal intensities on short T1 inversion recovery of muscle MRI. Of the 251 patients with MG, 23 were administered statins at the onset of MG. One late-onset MG patient experienced MG worsening after 4-wk treatment with atorvastatin. However, anti-HMGCR antibodies were not detected in the 251 MG patients except for one early-onset MG patient with no history of statin therapy. Anti-HMGCR antibodies are a relevant clinical marker of necrotizing myopathy with or without statin exposure, but they are not associated with the onset or deterioration of MG. Wolters Kluwer Health 2015-01-30 /pmc/articles/PMC4602975/ /pubmed/25634171 http://dx.doi.org/10.1097/MD.0000000000000416 Text en Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0 This is an open access article distributed under the Creative Commons Attribution-NonCommercial License, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be used commercially. http://creativecommons.org/licenses/by-nc/4.0 |
spellingShingle | 5300 Watanabe, Yurika Suzuki, Shigeaki Nishimura, Hiroaki Murata, Ken-ya Kurashige, Takashi Ikawa, Masamichi Asahi, Masaru Konishi, Hirofumi Mitsuma, Satsuki Kawabata, Satoshi Suzuki, Norihiro Nishino, Ichizo Statins and Myotoxic Effects Associated With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies: An Observational Study in Japan |
title | Statins and Myotoxic Effects Associated With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies: An Observational Study in Japan |
title_full | Statins and Myotoxic Effects Associated With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies: An Observational Study in Japan |
title_fullStr | Statins and Myotoxic Effects Associated With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies: An Observational Study in Japan |
title_full_unstemmed | Statins and Myotoxic Effects Associated With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies: An Observational Study in Japan |
title_short | Statins and Myotoxic Effects Associated With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies: An Observational Study in Japan |
title_sort | statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme a reductase autoantibodies: an observational study in japan |
topic | 5300 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602975/ https://www.ncbi.nlm.nih.gov/pubmed/25634171 http://dx.doi.org/10.1097/MD.0000000000000416 |
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