The serological hallmark of the altered immunological status of patients with systemic lupus erythematosus (SLE) is the presence of antibodies in the sera of these patients to variety of autoantigens, most notably DNA and complexes of DNA-histone. Our laboratory has engaged in a study of immune responses in SLE patients to a family of antigens which do not contain DNA but are small RNA protein particles. Precipitating antibodies to one or more of these antigens occur in 80% of unselected SLE patients. All of these antigens have been purified to chemical homogeneity by affinity chromatography methods and sensitive ELISA techniques adapted to measurement of specific antibodies. This proposal aims to study several aspects of the immune response to these RNAprotein antigens as well as some studies of idiotypes on anti-DNA molecules in SLE patients. The problems to be studied are (1) an analysis of the cellular basis of the association of the response to the antigen pairs Ro/SSA, La/SSB and nRNP, Sm. (2) Examination of anti-Ro/SSA antibodies from different SLE subsets for the presence of distinguishing molecular characteristics, including specific idiotype markers. (3) Search for evidence of participation of antibodies to the RNAprotein antigens in circulating immune complexes in SLE and Sjogren's patients. (4) Study of shared idiotypes on anti-DNA molecules in SLE sera and the study of autoanti-idiotypes in individual SLE patients studied longitudinally. (5) Age related production of specific autoantibodies in the SLE population. (6) Search for Ro/SSA antigen in neonatal skin and conducting tissue of the heart. Such studies should enhance our understanding of the production of these antibodies, their role in disease expression, and their relationship to the basic defect in immunoregulation characteristic of these patients.