PRESENCE OF ANTIBODIES TO DIFFERENT SUBUNITS OF REPLICATION PROTEIN-AIN AUTOIMMUNE SERA

A human cDNA expression library was used to investigate the nature of molecules recognized by serum from a patient with Sjogren syndrome tha t exhibits a mixed immunofluorescence pattern and reacts with multiple components on an immunoblot. The data demonstrated that this serum co ntains IgG antibodies specific for the 70- and 32-kDa subunits of repl ication protein A (RPA; RPA-70 and RPA-32, respectively), a highly con served multisubunit DNA binding protein. Affinity purification of seru m autoantibodies demonstrated a complete lack of cross-reactivity betw een RPA-70 and RPA-32, suggesting a direct participation of the native protein complex in the autoimmune response in this patient. Purified anti-RPA-70 and anti-RPA-32 antibodies labeled nuclear and cytoplasmic components in an immunofluorescence assay, suggesting that RPA is pre sent in both cellular compartments. Additional sera from 55 patients w ith different autoimmune conditions were screened against purified RPA -70 and RPA-32 recombinant proteins. One of these 55 sera was positive and reacted with only RPA-32. Twenty sera from healthy control indivi duals did not react with RPA. These results show that RPA is a target for autoantibodies in human autoimmune diseases, although its precise frequency, occurrence in other autoimmune diseases, and pathological s ignificance remain to be fully elucidated.