Skeletal Muscle Involvement in Antisynthetase Syndrome | Allergy and Clinical Immunology | JAMA Neurology | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Targoff  IN.  Autoantibodies in polymyositis.  Rheum Dis Clin North Am. 1992;18(2):455-482.PubMedGoogle Scholar
Mozaffar  T, Pestronk  A.  Myopathy with anti-Jo-1 antibodies: pathology in perimysium and neighbouring muscle fibres.  J Neurol Neurosurg Psychiatry. 2000;68(4):472-478.PubMedGoogle ScholarCrossref
Stenzel  W, Preuße  C, Allenbach  Y,  et al.  Nuclear actin aggregation is a hallmark of anti-synthetase syndrome-induced dysimmune myopathy.  Neurology. 2015;84(13):1346-1354.PubMedGoogle ScholarCrossref
Aouizerate  J, De Antonio  M, Bassez  G,  et al.  Myofiber HLA-DR expression is a distinctive biomarker for antisynthetase-associated myopathy.  Acta Neuropathol Commun. 2014;2:154.PubMedGoogle ScholarCrossref
Mescam-Mancini  L, Allenbach  Y, Hervier  B,  et al.  Anti-Jo-1 antibody-positive patients show a characteristic necrotizing perifascicular myositis.  Brain. 2015;138(pt 9):2485-2492.PubMedGoogle ScholarCrossref
Dalakas  MC.  Inflammatory muscle diseases.  N Engl J Med. 2015;373(4):393-394.PubMedGoogle ScholarCrossref
De Bleecker  JL, De Paepe  B, Aronica  E,  et al; ENMC Myositis Muscle Biopsy Study Group.  205th ENMC International Workshop: pathology diagnosis of idiopathic inflammatory myopathies part II 28-30 March 2014, Naarden, The Netherlands.  Neuromuscul Disord. 2015;25(3):268-272.PubMedGoogle ScholarCrossref
Stenzel  W, Goebel  HH, Aronica  E.  Review: immune-mediated necrotizing myopathies: a heterogeneous group of diseases with specific myopathological features.  Neuropathol Appl Neurobiol. 2012;38(7):632-646.PubMedGoogle ScholarCrossref
Suzuki  S, Yonekawa  T, Kuwana  M,  et al.  Clinical and histological findings associated with autoantibodies detected by RNA immunoprecipitation in inflammatory myopathies.  J Neuroimmunol. 2014;274(1-2):202-208.PubMedGoogle ScholarCrossref
Watanabe  Y, Uruha  A, Suzuki  S,  et al.  Clinical features and prognosis in anti-SRP and anti-HMGCR necrotising myopathy.  J Neurol Neurosurg Psychiatry. 2016;87(10):1038-1044.PubMedGoogle ScholarCrossref
van Swieten  JC, Koudstaal  PJ, Visser  MC, Schouten  HJ, van Gijn  J.  Interobserver agreement for the assessment of handicap in stroke patients.  Stroke. 1988;19(5):604-607.PubMedGoogle ScholarCrossref
Suzuki  S, Hayashi  YK, Kuwana  M, Tsuburaya  R, Suzuki  N, Nishino  I.  Myopathy associated with antibodies to signal recognition particle: disease progression and neurological outcome.  Arch Neurol. 2012;69(6):728-732.PubMedGoogle ScholarCrossref
Suzuki  S, Satoh  T, Yasuoka  H,  et al.  Novel autoantibodies to a voltage-gated potassium channel Kv1.4 in a severe form of myasthenia gravis.  J Neuroimmunol. 2005;170(1-2):141-149.PubMedGoogle ScholarCrossref
Ohnuki  Y, Suzuki  S, Shiina  T,  et al.  HLA-DRB1 alleles in immune-mediated necrotizing myopathy.  Neurology. 2016;87(18):1954-1955.PubMedGoogle ScholarCrossref
Targoff  IN, Trieu  EP, Miller  FW.  Reaction of anti-OJ autoantibodies with components of the multi-enzyme complex of aminoacyl-tRNA synthetases in addition to isoleucyl-tRNA synthetase.  J Clin Invest. 1993;91(6):2556-2564.PubMedGoogle ScholarCrossref
Meyer  A, Lefevre  G, Bierry  G,  et al; Club Rhumatismes et Inflammation.  In antisynthetase syndrome, ACPA are associated with severe and erosive arthritis: an overlapping rheumatoid arthritis and antisynthetase syndrome.  Medicine (Baltimore). 2015;94(20):e523.PubMedGoogle ScholarCrossref
Uruha  A, Suzuki  S, Suzuki  N, Nishino  I.  Perifascicular necrosis in anti-synthetase syndrome beyond anti-Jo-1.  Brain. 2016;139(pt 9):e50.PubMedGoogle ScholarCrossref
Aggarwal  R, Cassidy  E, Fertig  N,  et al.  Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients.  Ann Rheum Dis. 2014;73(1):227-232.PubMedGoogle ScholarCrossref
Hamaguchi  Y, Fujimoto  M, Matsushita  T,  et al.  Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: heterogeneity within the syndrome.  PLoS One. 2013;8(4):e60442.PubMedGoogle ScholarCrossref
Mahler  M, Miller  FW, Fritzler  MJ.  Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review.  Autoimmun Rev. 2014;13(4-5):367-371.PubMedGoogle ScholarCrossref
Nakashima  R, Imura  Y, Hosono  Y,  et al.  The multicenter study of a new assay for simultaneous detection of multiple anti-aminoacyl-tRNA synthetases in myositis and interstitial pneumonia.  PLoS One. 2014;9(1):e85062.PubMedGoogle ScholarCrossref
Uruha  A, Noguchi  S, Hayashi  YK,  et al.  Hepatitis C virus infection in inclusion body myositis: a case-control study.  Neurology. 2016;86(3):211-217.PubMedGoogle ScholarCrossref
Hida  A, Yamashita  T, Hosono  Y,  et al.  Anti-TIF1-γ antibody and cancer-associated myositis: a clinicohistopathologic study.  Neurology. 2016;87(3):299-308.PubMedGoogle ScholarCrossref
Allenbach  Y, Keraen  J, Bouvier  AM,  et al.  High risk of cancer in autoimmune necrotizing myopathies: usefulness of myositis specific antibody.  Brain. 2016;139(pt 8):2131-2135.PubMedGoogle ScholarCrossref
O’Hanlon  TP, Carrick  DM, Targoff  IN,  et al.  Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -Cw, -DRB1, and -DQA1 allelic profiles distinguish European American patients with different myositis autoantibodies.  Medicine (Baltimore). 2006;85(2):111-127.PubMedGoogle ScholarCrossref
Hervier  B, Devilliers  H, Stanciu  R,  et al.  Hierarchical cluster and survival analyses of antisynthetase syndrome: phenotype and outcome are correlated with anti-tRNA synthetase antibody specificity.  Autoimmun Rev. 2012;12(2):210-217.PubMedGoogle ScholarCrossref
Yamasaki  Y, Yamada  H, Nozaki  T,  et al.  Unusually high frequency of autoantibodies to PL-7 associated with milder muscle disease in Japanese patients with polymyositis/dermatomyositis.  Arthritis Rheum. 2006;54(6):2004-2009.PubMedGoogle ScholarCrossref
Uruha  A, Nishikawa  A, Tsuburaya  RS,  et al.  Sarcoplasmic MxA expression: a valuable marker of dermatomyositis.  Neurology. 2017;88(5):493-500.PubMedGoogle ScholarCrossref
Suzuki  S, Nishikawa  A, Kuwana  M,  et al.  Inflammatory myopathy with anti-signal recognition particle antibodies: case series of 100 patients.  Orphanet J Rare Dis. 2015;10:61.PubMedGoogle ScholarCrossref
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.


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.