Skeletal muscle involvement in antisynthetase syndrome

Eri Noguchi, Akinori Uruha, Shigeaki Suzuki, Kohei Hamanaka, Yuko Ohnuki, Jun Tsugawa, Yurika Watanabe, Jin Nakahara, Takashi Shiina, Norihiro Suzuki, Ichizo Nishino

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 analyzedin 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. MAINOUTCOMES ANDMEASURES 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.

Original languageEnglish
Pages (from-to)992-999
Number of pages8
JournalJAMA Neurology
Volume74
Issue number8
DOIs
Publication statusPublished - 2017 Aug 1

Fingerprint

Myositis
Amino Acyl-tRNA Synthetases
Skeletal Muscle
Antibodies
Muscle Weakness
Immunoprecipitation
HLA-DRB1 Chains
Anti-Idiotypic Antibodies
Interstitial Lung Diseases
Muscles
Extremities
Alleles
RNA
Neck Muscles
Raynaud Disease
Muscular Atrophy
Antisynthetase syndrome
Joint Diseases
Immunosuppressive Agents
Deglutition Disorders

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Noguchi, E., Uruha, A., Suzuki, S., Hamanaka, K., Ohnuki, Y., Tsugawa, J., ... Nishino, I. (2017). Skeletal muscle involvement in antisynthetase syndrome. JAMA Neurology, 74(8), 992-999. https://doi.org/10.1001/jamaneurol.2017.0934

Skeletal muscle involvement in antisynthetase syndrome. / Noguchi, Eri; Uruha, Akinori; Suzuki, Shigeaki; Hamanaka, Kohei; Ohnuki, Yuko; Tsugawa, Jun; Watanabe, Yurika; Nakahara, Jin; Shiina, Takashi; Suzuki, Norihiro; Nishino, Ichizo.

In: JAMA Neurology, Vol. 74, No. 8, 01.08.2017, p. 992-999.

Research output: Contribution to journalArticle

Noguchi, E, Uruha, A, Suzuki, S, Hamanaka, K, Ohnuki, Y, Tsugawa, J, Watanabe, Y, Nakahara, J, Shiina, T, Suzuki, N & Nishino, I 2017, 'Skeletal muscle involvement in antisynthetase syndrome', JAMA Neurology, vol. 74, no. 8, pp. 992-999. https://doi.org/10.1001/jamaneurol.2017.0934
Noguchi E, Uruha A, Suzuki S, Hamanaka K, Ohnuki Y, Tsugawa J et al. Skeletal muscle involvement in antisynthetase syndrome. JAMA Neurology. 2017 Aug 1;74(8):992-999. https://doi.org/10.1001/jamaneurol.2017.0934
Noguchi, Eri ; Uruha, Akinori ; Suzuki, Shigeaki ; Hamanaka, Kohei ; Ohnuki, Yuko ; Tsugawa, Jun ; Watanabe, Yurika ; Nakahara, Jin ; Shiina, Takashi ; Suzuki, Norihiro ; Nishino, Ichizo. / Skeletal muscle involvement in antisynthetase syndrome. In: JAMA Neurology. 2017 ; Vol. 74, No. 8. pp. 992-999.
@article{ff795e946f304e9e9e81eedfea6975f8,
title = "Skeletal muscle involvement in antisynthetase syndrome",
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 analyzedin 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. MAINOUTCOMES ANDMEASURES 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.",
author = "Eri Noguchi and Akinori Uruha and Shigeaki Suzuki and Kohei Hamanaka and Yuko Ohnuki and Jun Tsugawa and Yurika Watanabe and Jin Nakahara and Takashi Shiina and Norihiro Suzuki and Ichizo Nishino",
year = "2017",
month = "8",
day = "1",
doi = "10.1001/jamaneurol.2017.0934",
language = "English",
volume = "74",
pages = "992--999",
journal = "JAMA Neurology",
issn = "2168-6149",
publisher = "American Medical Association",
number = "8",

}

TY - JOUR

T1 - Skeletal muscle involvement in antisynthetase syndrome

AU - Noguchi, Eri

AU - Uruha, Akinori

AU - Suzuki, Shigeaki

AU - Hamanaka, Kohei

AU - Ohnuki, Yuko

AU - Tsugawa, Jun

AU - Watanabe, Yurika

AU - Nakahara, Jin

AU - Shiina, Takashi

AU - Suzuki, Norihiro

AU - Nishino, Ichizo

PY - 2017/8/1

Y1 - 2017/8/1

N2 - 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 analyzedin 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. MAINOUTCOMES ANDMEASURES 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.

AB - 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 analyzedin 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. MAINOUTCOMES ANDMEASURES 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.

UR - http://www.scopus.com/inward/record.url?scp=85027455349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027455349&partnerID=8YFLogxK

U2 - 10.1001/jamaneurol.2017.0934

DO - 10.1001/jamaneurol.2017.0934

M3 - Article

C2 - 28586844

AN - SCOPUS:85027455349

VL - 74

SP - 992

EP - 999

JO - JAMA Neurology

JF - JAMA Neurology

SN - 2168-6149

IS - 8

ER -