The clinical phenotype associated with myositis-specific and associated autoantibodies: a meta-analysis revisiting the so-called antisynthetase syndrome.
OBJECTIVE
To describe the clinical spectrum associated with aminoacyl-transfer RNA synthetase (ARS) autoantibodies in patients with idiopathic inflammatory myositis defined according to Peter and Bohan's criteria.


METHODS
Cohort studies were selected from MEDLINE and Embase up to August 2013. Two investigators independently extracted data on study design, patient characteristics, and clinical features (interstitial lung disease [ILD], fever, mechanic's hands [MH], Raynaud's phenomenon [RPh], arthralgia, sclerodactyly, cancer and dermatomyositis-specific rash) according to the presence of myositis-specific (anti-aminoacyl-transfer RNA synthetase [ARS], anti-signal recognition particle [anti-SRP] and anti-Mi2) and myositis-associated (anti-PM/Scl, anti-U1-RNP and anti-Ku) autoantibodies.


RESULTS
27 studies (3487 patients) were included in the meta-analysis. Arthralgia (75%, CI 67-81) and ILD (69%, CI 63-74) were the most prevalent clinical signs associated with anti-ARS autoantibodies. Anti-Mi2 and anti-SRP autoantibodies were associated with few extramuscular signs. ARS autoantibodies were identified in 13% of patients with cancer-associated myositis (5-25). Patients with non-anti-Jo1 ARS had greater odds of presenting fever (RR 0.63, CI 0.52-0.90) and ILD (RR 0.87, CI 0.81-0.93) compared to those with anti-Jo1 autoantibodies. The frequencies of myositis (RR 1.60, CI 1.38-1.85), arthralgia (RR 1.52, CI 1.32-1.76) and MH (RR 1.47, CI 1.11-1.94) were almost 50% higher in patients with anti-Jo1 compared to non-anti-Jo1 ARS autoantibodies. Patients with anti-PM/Scl differed from those with anti-ARS autoantibodies by a greater prevalence of RPh (RR 0.70, CI 0.53-0.94) and sclerodactyly (RR 0.47, CI 0.25-0.89). ILD was less frequent in patients with anti-U1-RNP autoantibodies (RR 3.35, CI 1.07-10.43). No difference was observed between anti-ARS and myositis-associated autoantibodies for other outcomes.


CONCLUSIONS
The presence of anti-ARS autoantibodies delimits a heterogeneous subset of patients with a high prevalence of myositis, MH, arthralgia in anti-Jo1 patients, and RPh and fever in non-anti-Jo1 patients. The clinical signs of populations positive for anti-PM/Scl and anti-ARS autoantibodies largely overlap, especially with regard to ILD, challenging the clinical delimitation of the antisynthetase syndrome.
Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Claude Bernard University Lyon 1, University of Lyon, France; UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, CNRS, Claude Bernard University Lyon 1, University of Lyon, France.
Jean-Christophe
JC
Lega
Department of Immunology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Claude Bernard University Lyon 1, University of Lyon, France.
Nicole
N
Fabien
Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Claude Bernard University Lyon 1, University of Lyon, France.
Quitterie
Q
Reynaud
Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Claude Bernard University Lyon 1, University of Lyon, France.
Isabelle
I
Durieu
Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Claude Bernard University Lyon 1, University of Lyon, France.
Stéphane
S
Durupt
Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Claude Bernard University Lyon 1, University of Lyon, France.
Marine
M
Dutertre
National Reference Centre for Rare Pulmonary Diseases, Department of Respiratory Medicine, Louis Pradel Hospital, Hospices Civils de Lyon, UMR 754, Claude Bernard University Lyon 1, University of Lyon, France.
Jean-François
JF
Cordier
National Reference Centre for Rare Pulmonary Diseases, Department of Respiratory Medicine, Louis Pradel Hospital, Hospices Civils de Lyon, UMR 754, Claude Bernard University Lyon 1, University of Lyon, France.
Vincent
V
Cottin
D000604:Amino Acyl-tRNA Synthetases / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D015331:Cohort Studies; D006801:Humans; D009220:Myositis / Q000276:immunology* / Q000401:mortality; D010641:Phenotype
D001323:Autoantibodies; D000604:Amino Acyl-tRNA Synthetases
Anti-PM/Scl autoantibodies; Anti-aminoacyl-tRNA synthetase autoantibodies; Interstitial lung disease; Myositis; Systemic sclerosis