AUTOANTIBODIES TO RNA-POLYMERASE-II ARE COMMON IN SYSTEMIC LUPUS-ERYTHEMATOSUS AND OVERLAP SYNDROME - SPECIFIC RECOGNITION OF THE PHOSPHORYLATED (IIO) FORM BY A SUBSET OF HUMAN SERA

Autoantibodies to RNA polymerases (RNAP) I, II, and III are reported t o be highly specific for the diagnosis of scleroderma (systemic sclero sis, SSc). In the present study, the specificity of autoantibodies to RNAP I and III for SSc was confirmed by immunoprecipitation of S-35-la beled proteins. However, we report here the previously unrecognized pr oduction of anti-RNAP II autoantibodies by 9-14% of patients with SLE and mixed connective tissue disease/overlap syndrome. 12 out of 32 ant i-RNAP n. positive sera (group 1) immunoprecipitated a diffuse 220-240 -M) band identified as the largest subunit of RNAP II whereas the rema ining 20 (group 2) immunoprecipitated preferentially the 240-kD phosph orylated (IIo) form of the large subunit, After pulse labeling, group 1 sera immunoprecipitated only the 220-kD (IIa) RNAP II subunit, where as the diffuse IIa/IIo band plus the 145-kD second largest RNAP II sub unit (IIc) were immunoprecipitated after several hours of cold chase, suggesting that these sera recognized primarily the largest subunit of RNAP II. Group 2 sera recognized the IIc subunit after pulse labeling , and immunoprecipitated the IIc and IIo, but not the IIa, subunits af ter cold chase. Although it has been suggested that autoantibodies to RNAP II are usually accompanied by anti-RNAP I/III in SSc, all but one of the anti-RNAP II positive sera from SLE or mixed connective tissue disease/overlap syndrome patients, as well as most of the SSc sera, w ere negative for anti-RNAP I/III. Moreover, in contrast to previous re ports suggesting that anti-RNAP antibodies rarely coexist with other S Sc subset marker antibodies, anti-RNAP II antibodies were often accomp anied by anti-Ku, anti-nRNP, or anti-topoisomerase I autoantibodies in the present study. We conclude that autoantibodies to RNAP II are not a specific marker for SSc, whereas autoantibodies to RNAP I/III are a ssociated primarily with SSc. In addition, we have identified two dist inctive patterns of RNAP II antigen recognition by autoantibodies, one of them characterized by specific recognition of the transcriptionall y active (phosphorylated) form of RNAP II. The clinical significance o f these different patterns remains to be determined.