title: Statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: an observational study in Japan.
abstract: 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.
authors: From the Department of Neurology, Keio University School of Medicine (YW, SS, NS); Department of Neuromuscular Research, National Institute of Neuroscience, and Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo (HN, IN); Department of Neurology, Wakayama Medical University, Wakayama (K-YM); Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Hiroshima (TK); Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (MI); Department of Neurology, Mie University Graduate School of Medicine, Tsu (MA); Department of Neurology, University of Toyama, Toyama (HK); Department of Neurology, Graduate School of Medicine, Chiba University, Chiba (SM); and Department of Neurology, Asahikawa Red Cross Hospital, Asahikawa, Japan (SK).
authors: Yurika
authors: Y
authors: Watanabe
authors: Shigeaki
authors: S
authors: Suzuki
authors: Hiroaki
authors: H
authors: Nishimura
authors: Ken-Ya
authors: KY
authors: Murata
authors: Takashi
authors: T
authors: Kurashige
authors: Masamichi
authors: M
authors: Ikawa
authors: Masaru
authors: M
authors: Asahi
authors: Hirofumi
authors: H
authors: Konishi
authors: Satsuki
authors: S
authors: Mitsuma
authors: Satoshi
authors: S
authors: Kawabata
authors: Norihiro
authors: N
authors: Suzuki
authors: Ichizo
authors: I
authors: Nishino
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000276:immunology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007564:Japan; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009220:Myositis / Q000188:drug therapy / Q000276:immunology*; D009336:Necrosis; D009460:Neurologic Examination
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006903:Hydroxymethylglutaryl CoA Reductases
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