Eri Noguchi1, Akinori Uruha2,3, Shigeaki Suzuki1, Kohei Hamanaka2, Yuko Ohnuki4, Jun Tsugawa5, Yurika Watanabe1, Jin Nakahara1, Takashi Shiina4, Norihiro Suzuki1, Ichizo Nishino2. 1. Department of Neurology, Keio University School of Medicine, Tokyo, Japan. 2. Department of Neuromuscular Research, National Institute of Neuroscience, and Department of Genome Medicine Development, Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo, Japan. 3. Pierre 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. 4. Department of Molecular Life Science, Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Isehara-shi, Kanagawa, Japan. 5. Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan.
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.
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.
Authors: Yoshioki Yamasaki; Hidehiro Yamada; Toshiko Nozaki; Jun Akaogi; Cody Nichols; Robert Lyons; Anthony Chin Loy; Edward K L Chan; Westley H Reeves; Minoru Satoh Journal: Arthritis Rheum Date: 2006-06
Authors: Werner Stenzel; Corinna Preuße; Yves Allenbach; Debora Pehl; Reimar Junckerstorff; Frank L Heppner; Kay Nolte; Eleonora Aronica; Veronika Kana; Elisabeth Rushing; Udo Schneider; Kristl G Claeys; Olivier Benveniste; Joachim Weis; Hans H Goebel Journal: Neurology Date: 2015-03-06 Impact factor: 9.910
Authors: Corinna Preuße; Barbara Paesler; Christopher Nelke; Derya Cengiz; Thomas Müntefering; Andreas Roos; Damien Amelin; Yves Allenbach; Akinori Uruha; Carsten Dittmayer; Andreas Hentschel; Marc Pawlitzki; Sarah Hoffmann; Sara Timm; Sarah Leonard Louis; Nora F Dengler; Heinz Wiendl; Jan D Lünemann; Albert Sickmann; Baptiste Hervier; Sven G Meuth; Udo Schneider; Anne Schänzer; Sabine Krause; Stylianos Tomaras; Eugen Feist; Rebecca Hasseli; Hans-Hilmar Goebel; Laure Gallay; Nathalie Streichenberger; Olivier Benveniste; Werner Stenzel; Tobias Ruck Journal: Acta Neuropathol Date: 2022-05-25 Impact factor: 15.887