IDENTIFICATION OF AUTOANTIBODIES TO RNA POLYMERASE-II - OCCURRENCE INSYSTEMIC-SCLEROSIS AND ASSOCIATION WITH AUTOANTIBODIES TO RNA POLYMERASE-I AND POLYMERASE-III

In this study, autoantibodies to RNA polymerase II from sera of patien ts with systemic sclerosis have been identified and characterized. The se antibodies immunoprecipitated polypeptides of 220 kD (IIA) and 145 kD (IIC), the two largest subunits of RNA polymerase II, and bound bot h subunits in immunoblots. These polypeptides were immunoprecipitated by the anti-RNA polymerase II monoclonal antibody 8WG16, which recogni zes the carboxyl-terminal domain of the 220-kD subunit, and their iden tity to the proteins bound by human sera was confirmed in immunodeplet ion studies. Sera with anti-RNA polymerase II antibodies also immunopr ecipitated proteins that were consistent with components of RNA polyme rases I and III. In vitro transcription experiments showed that the hu man antibodies were an effective inhibitor of RNA polymerase II activi ty. In indirect immunofluorescence studies, anti-RNA polymerase II aut oantibodies stained the nucleoplasm, as expected from the known locati on of RNA polymerase II, and colocalized with the anti-RNA polymerase II monoclonal antibody. The human sera also stained the nucleolus, the location of RNA polymerase I. From a clinical perspective, these anti bodies were found in 13 of 278 patients with systemic sclerosis, inclu ding 10 with diffuse and three with limited cutaneous disease, but wer e not detected in sera from patients with other connective tissue dise ases and from normal controls. We conclude that anti-RNA polymerase II antibodies are specific to patients with systemic sclerosis, and that they are apparently associated with antibodies to RNA polymerases I a nd III. These autoantibodies may be useful diagnostically and as a pro be for further studies of the biological function of RNA polymerases.