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 PARTICIPANTSIn 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 MEASURESThe main outcomes were muscle manifestations and histological findings. Predisposing factors, extramuscular symptoms, and follow-up information were also studied. RESULTSOf 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 RELEVANCEAlthough 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.

Diagnostic potential of sarcoplasmic myxovirus resistance protein A expression in subsets of dermatomyositis

“…ASS is associated with anti‐aminoacyl transfer RNA synthetase autoantibodies and clinically with myositis, characteristic skin lesion (mechanic's hands are typical, but heliotrope rash and Gottron's signs/papules can also be seen), Raynaud phenomenon, interstitial lung disease, arthritis/arthralgia, and systemic symptom such as fever . Some of the clinical features and a pathological finding of perifascicular reinforcement of human leucocyte antigen (HLA)‐ABC [major histocompatibility complex (MHC) class I] expression on the sarcoplasm are shared with DM, yet ASS has a unique myopathological phenotype.…”

“…We selected 30 patients with ASS [65 (13–85) years of age at biopsy: median and range, sex ratio (male:female) 1:1.7], 9 with IMNM [four positive for anti‐signal recognition particle (SRP) and five positive for anti‐3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGCR) autoantibodies] [39 (10–61) years of age, 1:0.8], 5 with IBM [63 (57–69) years of age, 1:0.7] and 7 with muscular dystrophy (three with dystrophinopathy and four with dysferlinopathy) [39 (6–80) years of age, 1:0.4]. The autoantibodies in their sera were measured by means of RNA and protein immunoprecipitation for anti‐aminoacyl transfer RNA synthetase antibodies (anti‐OJ, ‐EJ and ‐KS), addressable laser bead immunoassay for anti‐TIF1‐γ, ‐SRP and ‐HMGCR antibodies or line‐immunoassay (D‐Tek, Mons, Belgium) for the others as previously described . We chose subjects in a consecutive manner within each disease group and investigated their frozen skeletal muscle samples that were first biopsied.…”

Clinical manifestations of skin, lung and muscle diseases in dermatomyositis positive for anti‐aminoacyl tRNA synthetase antibodies

“…Alternatively, the rather high incidence of fasciitis in patients with ASS may account for the different inflammatory processes in the subtypes of dermatomyositis: type 1 interferon‐mediated myositis, and perifascicular necrosis rather characteristic for ASS . It has been reported that patients with myopathy with “perimysial pathology” showed a selective increase of ALD, and the clinical symptoms of such patients are similar to ASS .…”

Reply

“…In contrast, inflammatory infiltrates (e.g., CD8+ cells and a lesser number of macrophages) surround and invade non‐necrotic muscle fibers expressing major histocompatibility complex class I antigens within the fascicles in patients with PM . In their study of antisynthetase syndrome, Noguchi et al observed that mononuclear cells infiltrated into perimysial sites (usually perivascular sites) but did not surround the endomysium or invade into non‐necrotic muscle fibers within the fascicles, as is typically observed in PM. Basically, the sites of inflammatory infiltrates in antisynthetase syndrome are similar to those in DM, but not in PM.…”