Clinical and serological associations with anti-RNA polymerase antibodies in systemic sclerosis

There are three classes of RNA polymerase enzyme (RNAPs I, II and III). In systemic sclerosis (SSc), three main groups of anti-RNAP sera have been cha racterized by radioimmunoprecipitation techniques: anti-RNAP I/III sera, an ti-RNAP I/II/III sera, and a group precipitating both RNAP II and topoisome rase I (topo I). Some sera in this third group precipitate the phosphorylat ed (IIO) form of RNAP II in the absence of the unphosphorylated (IIA) form. Certain other antinuclear antibodies (ANA) have also been detected in anti -RNAP IIO/IIA/topo I and anti-RNAP IIO/topo I sera. In the present study of 155 SSc patients, clinical features of individuals from each of these anti body groups were assessed and compared with those of patients from other au toantibody-defined groups. The anti-RNAP I/II/III antibody specificity was closely associated with the presence of diffuse cutaneous SSc (dc-SSc) (77. 8%; cf. remaining group, 12.4%; P<0.001; relative risk (RR) 6.3). Patients with anti-RNAP I/III antibodies also had an increased incidence of dc-SSc, but this was not significant (42.9%; cf. remainder, 15.7%). Anti-RNAP(+) pa tients had a significantly increased incidence of renal involvement (29.0%, cf. remainder, 11.3%; P<0.05; RR 2.6), with 40% of anti-RNAP I/II/III pati ents having renal disease. Meanwhile, the presence of anti-centromere antib odies (ACA) was associated with limited cutaneous SSc (lc-SSc) (100.0%; cf. remainder, 75.3%; P , 0.005), together with reduced incidences of both ren al disease (2.4%, cf. remainder, 22.1%: P<0.01) and pulmonary fibrosis (21. 4%, cf. remainder, 52.3%; P<0.005; RR 1.9). Anti-topo I antibodies were ass ociated with the presence of pulmonary fibrosis (69.7%; cf. remainder, 32.6 %; P<0.001; RR 2.1). A majority of anti-topo I sera were from 1c-SSc patien ts, regardless of whether anti-topo I antibodies occurred alone (75.0%) or together with anti-RNAP IIO + IIA antibodies (75.0%), and this was similar to the remainder (86.5%; NS). However, when anti-topo I+ patients were comp ared with the ACA group, and then with all anti-RNAP I+ patients (37.5% 1c- SSc), significant differences were found in the occurrence of dc- versus 1c -SSc (P <0.005 and P<0.05, respectively). In conclusion, these results conf irm that there are three main groups of SSc sera, each characterized by the presence of a mutually exclusive SSc-specific autoantibody (ACA, anti-topo I or anti-RNAP I), and distinguished by patterns of cutaneous involvement and specific clinical features. It appears that, in each of the three group s of SSc patients, distinct pathological processes are occurring, which art : responsible for the characteristic symptoms, for the modification of part icular autoantigens and, consequently, for the production of particular aut oantibodies. Based on these data, together with our previous results, it is further hypothesized that anti-RNAP II antibodies may be produced in the c ontext of two different immune response pathways.