Novel Autoantibodies that recognize native transfer RNAs in patients with systemic rheumatic diseases

Autoantibodies directed against aminoacyl-tRNA synthetases are well described in adult polymyositis/dermatomyositis. However, the characteristics of antibodies against other tRNA and tRNA-associated proteins have not been well defined. In this study, we identified novel autoantibodies to total tRNAs in patients with systemic rheumatic diseases and characterized the structure that was recognized by anti-tRNA antibodies. We identified fifteen patients sera that immunoprecipitated the deproteinized cognate tRNA. Two of them were identified as having previously well-defined anti-PL-12 antibodies. Three of the remaining 13 patient sera immunoprecipitated naked tRNA of E. coli. To investigate the antibody binding site on tRNAs, we have used in vitro transcripts from cDNAs encoding wild type tRNAs of E. coli and their synthesized mutants. These sera revealed different reactivity to mutated tRNAs. Eleven of these 13 patients met disease specific criteria for: SLE (3 patients), Sjogren's syndrome (6), or SLE/Sjogren's syndrome overlap (2). In addition, fever, Raynaud's phenomenon, and non-erosive polyarthritis, were frequently found in these patients. In summary, we have identified novel antibodies to tRNAs which appear to be quite common, and distinct from previously described anti-aminoacyl-tRNA synthetase antibodies.