JAMA Neurol. 2017 Aug 1;74(8):992-999. doi: 10.1001/jamaneurol.2017.0934.

Skeletal Muscle Involvement in Antisynthetase Syndrome.


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.


Antisyntthetase syndromeは筋炎、関節性肺炎、皮疹、関節炎、レイノー現象等の臨床症状を特徴とした、ARS抗体陽性を前提とした疾患概念であるが、炎症性筋疾患には含まれていない。このため炎症性筋疾患としてのARS症候群を確立するため患者の筋病理および血清抗体についてコホート研究をおこなった。 2010年から2014年にかけて日本の多施設の炎症性筋疾患患者460人を対象に、筋病理、血清を収集し解析を行ったところ、51人(11.1%)の患者が抗ARS抗体陽性であった。この患者群では、四肢の筋力低下、重度の筋力低下、頸部の筋力低下、嚥下障害、筋萎縮等の症状が認められた。抗OJ抗体陽性例は重症であったが、抗ARS抗体陽性患者の臨床像は全体的に均一であった。病理では壊死像が最も特徴的で24人(47%)に認められた。 治療反応性は免疫抑制剤による治療が最も反応が良好であった。 間質性肺炎は筋炎よりもより予後に関与する因子であった。 このようにARS症候群の臨床、病理像は炎症性筋疾患が主体である。

PMID:  28586844