NOVEL AUTOANTIBODIES DIRECTED AGAINST THE COMMON TERTIARY CONFIGURATION OF TRANSFER-RNA IN A PATIENT WITH INTERSTITIAL LUNG-DISEASE

Objective. TO identify and characterize a novel autoantibody, anti-WS, that binds total transfer RNA (tRNA), Methods. Serum from patient WS, who had polyarthritis, Sjogren's syndrome, Raynaud's phenomenon, and interstitial pulmonary fibrosis, was used in this study. Characteristi cs of anti-WS and antibody-reactive determinants of tRNA were investig ated by P-32 immunoprecipitation using Beta cell RNA and deletion muta nts of tRNA transcribed ire vitro. Results, WS serum produced nucleola r and cytoplasmic staining on indirect immunofluorescence. P-32 immuno precipitation assays demonstrated that this serum immunoprecipitated t otal tRNAs and 5.8S and 5S ribosomal RNAs from P-32-labeled HeLa cell extract, When deproteinized RNA was used as antigen source, total tRNA s were still precipitated by WS serum. An immunoprecipitation study, u sing various deletion mutants of Escherichia coli tRNA, demonstrated t hat both D and T psi C loops were needed for antibody binding, Substit ution of nucleotide (15)G with (18)A of E coli tRNA(Trp), which is ess ential in the formation of the tertiary ''L'' shape of tRNA, inhibited binding by anti-WS antibodies. Conclusion. Anti-WS antibodies are nov el autoantibodies directed against tRNAs, The antibody binding site is the common L-shaped tertiary structure conformed by the D loop and T psi C loop of tRNA, suggesting that the antibodies are induced by a co nserved sequence among all species, Furthermore, these antibodies coul d be a marker for a newly recognized subset of connective tissue disea se.