AUTOANTIBODIES IN HUMAN ANTI-RO SERA SPECIFICALLY RECOGNIZE DEPROTEINIZED HY5 RO RNA

We report the existence of a novel autoantibody specificity linked to anti-Ro antibodies. Sera from two patients with anti-Ro ribonucleoprot ein (RNP) antibodies also contained antibodies that immunoprecipitated specifically either the deproteinized RNA component of the Ro(hY5) RN P particle, or intact in vitro transcribed hY5 RNA. No serum recognize d specifically the other hY RNAs. A mutant hY5 RNA with additional nuc leotides (nt) at both extremities was not immunoprecipitated, possibly because of altered secondary structure. Following digestion of hY5 RN A with ribonuclease T1, the smallest immunoprecipitable RNA fragments were 27 and 31 nt long, and respectively mapped to the 5' and 3' ends of hY5 RNA, excluding the La-binding region. Base pairing between the 27 and 31 nt long fragments was required for recognition by antibodies . Our data indicate that the epitope bound by anti-hY5 RNA antibodies is conformational. We have previously reported that most anti-Ro sera contain a population of antibodies specific for the Ro(hY5) RNP. Since antibodies to the deproteinized hY RNAs within anti-Ro sera are also restricted to anti-hY5 RNA, a direct role for the human-specific Ro(hY 5) particles in the immunization process leading to the production of anti-Ro antibodies is suggested.