ASSOCIATION OF AUTOANTIBODIES TO TOPOISOMERASE-I AND THE PHOSPHORYLATED (IIO) FORM OF RNA-POLYMERASE-II IN JAPANESE SCLERODERMA PATIENTS

Autoantibodies to RNA polymerases (RNAP) I and III are highly specific for scleroderma (SSc), whereas autoantibodies to RNAP II are associat ed with systemic lupus erythematosus (SLE) and overlap syndromes, as w ell as SSc. The specificities of autoantibodies to RNAP I, II, and III in 129 SSc sera were investigated in the present study. Immunoprecipi tation and pulse-chase analysis demonstrated several patterns of autoa ntibody recognition of RNAPs. Some sera immunoprecipitated RNAP II onl y after its largest subunit was phosphorylated, suggesting that they c ontained autoantibodies that recognized an epitope carrying a phosphoa mino acid. Autoantibody recognition of all three classes of RNAPs was influenced strongly by race. Although in SLE, autoantibodies to the ph osphorylated form of RNAP II (RNAP IIO) were identified in all races, in SSc, these autoantibodies were seen in 21% of Japanese and 5% of Bl ack patients, but never in Caucasians. A striking association of anti- RNAP IIO with anti-topoisomerase I (topo I) autoantibodies was found i n Japanese and Black SSc, but not SLE, patients. However, anti-topo I Abs were not associated with anti-RNAP IIO in Caucasians. Japanese SSc patients who were positive for both anti-RNAP IIO and anti-topo I Abs had a significantly higher frequency of diffuse disease, pigmentation changes, flexion contractures, and acro-osteolysis than patients havi ng autoantibodies to topo I alone, and were diagnosed at a younger age (p < 0.05). These data suggest that genetic factors (possibly HLA-lin ked) influence autoantibody specificity, and that different autoantibo dy fine specificities may either cause, or be predictive of, different clinical outcomes.