Autoantibodies to glycyl–transfer RNA synthetase in myositis. Association with dermatomyositis and immunologic heterogeneity

Abstract

Objective. To elucidate the clinical significance and immunologic heterogeneity of anti–glycyl–transfer RNA (tRNA) synthetase antibodies in polymyositis/dermatomyositis (PM/DM). Methods. Sera from 345 patients with rheumatic diseases, including 91 with myositis, were examined using immunoprecipitation assays. Autoantibodies to aminoacyl‐tRNA synthetases were further analyzed with 2‐dimensional RNA fractionation and via inhibition of in vitro aminoacylation. Results. Serum from 1 patient with DM and interstitial lung disease immunoprecipitated glycyl‐tRNA synthetase along with only 1 of 4 associated tRNAs, in comparison with control anti–glycyl‐tRNA synthetase antibodies, which bound the enzyme along with all 4 associated tRNAs. Immunoblotting findings and a lack of in vitro inhibition aminoacylation of tRNA^gly by serum from this patient also suggested differences between the epitope specificity of this serum and that of other sera with anti–glycyl‐tRNA synthetase antibodies. Conclusion. This identification of antibodies to glycyl‐tRNA synthetase from a patient with DM underscores the association of this specificity with the disease. The finding that these antibodies bound an epitope outside the active site of the synthetase enzyme, in contrast to most anti–aminoacyl‐tRNA synthetases, emphasizes the immunologic heterogeneity of these autoantibodies.