Skeletal Muscle Involvement in Antisynthetase Syndrome | Allergy and Clinical Immunology | JAMA Neurology | JAMA Network
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Original Investigation
August 2017

Skeletal Muscle Involvement in Antisynthetase Syndrome

Author Affiliations
  • 1Department of Neurology, Keio University School of Medicine, Tokyo, Japan
  • 2Department of Neuromuscular Research, National Institute of Neuroscience, and Department of Genome Medicine Development, Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo, Japan
  • 3Pierre and Marie Curie University–Paris VI (UPMC), National Institute of Health and Medical Research (INSERM), Mixed Research Unit (UMR) 974, Center of Research in Myology, Institute of Myology, Pitié-Salpêtrière University Hospital, Paris, France
  • 4Department of Molecular Life Science, Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Isehara-shi, Kanagawa, Japan
  • 5Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan
JAMA Neurol. 2017;74(8):992-999. doi:10.1001/jamaneurol.2017.0934
Key Points

Question  What are the features of myositis in patients with antisynthetase syndrome?

Findings  In this cohort study of 460 patients with idiopathic inflammatory myopathies, 51 (11.1%) had anti-aminoacyl transfer RNA synthetase antibodies. Autoantibody detection was consistent between RNA immunoprecipitation and line blot assay except for anti-OJ antibodies, which were associated with severe muscle involvement.

Meaning  Antisynthetase syndrome is a clinical and histological subset among idiopathic inflammatory myopathies.

Abstract

Importance  Antisynthetase syndrome, characterized by myositis, interstitial lung disease, skin rash, arthropathy, and Raynaud phenomenon, is a clinical entity based on the presence of aminoacyl transfer RNA synthetase (ARS) antibodies in patients’ serum. However, antisynthetase syndrome is not included in the histological subsets of idiopathic inflammatory myopathies.

Objective  To elucidate the clinical features of myositis in patients with antisynthetase syndrome.

Design, Setting, and Participants  In this cohort study, muscle biopsy and blood samples were collected from 460 patients with idiopathic inflammatory myositis from various regional referral centers throughout Japan between October 2010 and December 2014. Data were analyzed in March 2016.

Exposures  Six different anti-ARS antibodies were detected in serum by RNA immunoprecipitation. Line blot assay and protein immunoprecipitation were also performed. HLA-DRB1 alleles were genotyped.

Main Outcomes and Measures  The main outcomes were muscle manifestations and histological findings. Predisposing factors, extramuscular symptoms, and follow-up information were also studied.

Results  Of 460 patients with idiopathic inflammatory myopathies, 51 (11.1%) had anti-ARS antibodies. Of this subset, 31 (61%) were women, with a mean (SD) age at disease onset of 60.2 (16.1) years. Among 6 different anti-ARS antibodies, only 1—the anti-OJ antibody—was not detected by line blot assay but by RNA immunoprecipitation. There were no significant HLA-DRB1 alleles associated with anti-ARS antibodies. All 51 patients presented with muscle limb weakness; 14 (27%) had severe limb weakness, 17 (33%) had neck muscle weakness, 15 (29%) had dysphagia, and 15 (29%) had muscle atrophy. Although patients with anti-OJ antibodies showed severe muscle weakness, the clinical presentations of antisynthetase syndrome were relatively homogeneous. In histology, perifascicular necrosis, the characteristic finding of antisynthetase syndrome, was found in 24 patients (47%). Myositis with anti-ARS antibodies responded to the combination of immunosuppressive therapy with favorable outcomes. Interstitial lung disease, found in 41 patients (80%), was more closely associated with mortality than myositis.

Conclusions and Relevance  Although clinical presentations of antisynthetase syndrome were relatively homogeneous, anti-OJ antibodies were associated with severe muscle involvement. Antisynthetase syndrome is a clinical and histological subset among idiopathic inflammatory myopathies.

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