Anti-transfer RNA antibodies in two patients with pulmonary fibrosis, Raynaud's phenomenon and polyarthritis

Patient W.S. (a 61-year-old woman) and patient T.M. (a 41-year-old man) developed recurrent fevers, polyarthritis, Raynaud's phenomenon and interstitial pulmonary fibrosis without apparent polymyositis. From HeLa cell extracts, sera from both patients immunoprecipitated all species of intact and deproteinised tRNAs. To identify the antibody binding site more precisely, tRNAs transcribed in vitro from cloned Escherichia coli tRNA genes and various mutants were prepared and used as antigens for immunoprecipitation. When the TψC loop, or the D loop were deleted, such mutants were not bound by both sera, suggesting that the D and TψC loops were required for antibody binding. Abrogation of tRNA binding occurred when 18 G of tRNA Trp was replaced with 18 A to break the tertiary L-shape structure of tRNA. These results strongly suggest that sera from W.S. and T.M. recognise the tertiary conformation of L-shaped tRNA which is constructed with both D and TψC loops. These autoantibodies may also serve as a marker for a new subset of patients with connective tissue diseases that is distinct from anti-aminoacyl-tRNA synthetase syndrome.