AUTOANTIBODIES TO GLYCYL-TRANSFER RNA-SYNTHETASE IN MYOSITIS - ASSOCIATION WITH DERMATOMYOSITIS AND IMMUNOLOGICAL HETEROGENEITY

Objective. To elucidate the clinical significance and immunologic hete rogeneity 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 usi ng immunoprecipitation assays, Autoantibodies to aminoacyl-tRNA synthe tases were further analyzed with 2-dimensional RNA fractionation and v ia inhibition of in vitro aminoacylation. Results. Serum from 1 patien t with DM and interstitial lung disease immunoprecipitated glycyl-tRNA synthetase along with only 1 of 4 associated tRNAs, in comparison wit h control anti-glycyl-tRNA synthetase antibodies, which bound the enzy me along with all 4 associated tRNAs, Immunoblotting findings and a la ck of in vitro inhibition aminoacylation of tRNA(gly) by serum from th is 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-tR NA synthetase from a patient with DM underscores the association of th is specificity with the disease, The finding that these antibodies bou nd an epitope outside the active site of the synthetase enzyme, in con trast to most anti-aminoacyl-tRNA synthetases, emphasizes the immunolo gic heterogeneity of these autoantibodies.