Clinical heterogeneity and prognostic features of South Australian patients with anti-synthetase autoantibodies

Abstract

Aims: To determine the clinical, serological and prognostic features of patients with autoantibodies against three aminoacyl-transfer RNA synthetases (ARS), namely Jo-1 (histidyl-tRNA synthetase), PL-7 (threonyl-tRNA synthetase) and PL-12 (alanyl-tRNA synthetase) in South Australia. Methods: Patients with autoantibodies against ARS detected by line immunoassay (anti-Jo1, anti-PL7, anti-PL12) or enzyme-linked immunosorbent assay (anti-Jo1) were identified from existing laboratory databases for the period 1994 to 2009. Demographic, clinical and serological data were obtained by retrospective review of patients’ medical records and laboratory databases. Results: Forty two patients with autoantibodies were identified (anti-Jo1=37, anti-PL7=4, anti-PL12=1). Females were more commonly affected than males (M:F=12:30). Twenty one patients had polymyositis (anti-Jo1=17, anti-PL7=4), seven dermatomyositis (anti-Jo1=6, anti-PL12=1), ten overlap syndrome (anti-Jo1=10; lupus=4, scleroderma=3, Sjögren’s syndrome=2 and rheumatoid arthritis=2) and four had interstitial lung disease (ILD) only (anti-Jo1=4). ILD was present in 69%, polyarthritis in 59% and positive anti-nuclear antibody (ANA) in 43% of patients. Concurrence of autoantibodies against Ro-52 with Jo-1 was seen in twelve patients. The mean follow up period was 8.3 years (95% CI 5.8-10.8) with twelve deaths. Poor prognostic indicators were age of onset > 60 years (p=0.001), cancer (p=0.002), negative ANA (p=0.006) and negative autoantibodies to extractable nuclear antigens (p=0.02). Conclusions: Patients with autoantibodies against ARS present with varied clinical features and occasionally with isolated lung involvement (amyopathic ILD). Older age of onset, malignancy and negative immunologic tests are predictors of poor prognosis. Concurrence of autoantibodies against Jo-1 and Ro-52 may reflect a coupling effect during generation of autoimmunity.