Nephritis is a complication of systemic lupus erythematosus (SLE) that seriously affects prognosis. Predicting its occurrence and severity and monitoring its progress are of major clinical interest. The pathogenesis of lupus nephritis is thought to be mediated by immune complexes; the major system contributing to morbidity involves native DNA and its cognate antibodies. Other contributing systems include Ro/SSA anti-Ro/SSA immune complexes as well as Sm-anti-Sm immune complexes. It is now apparent that the Ro/SSA antigen is isomorphic with four different antigenic moieties being recognized. Lymphocytes and red cells each contain two forms: 60 and 52 kDa molecules in the lymphocytes, and 60 and 54 kDa molecules in red cells. Only 50% of SLE patients who produce anti-Ro/SSA develop nephritis and fine specificity studies by Western blot reveal that the risk for nephritis in those who produce principally anti-RBC 60 kDa antibody is very high while those who produce principally anti-RBC 54 kDa antibody is very low. It has also become apparent that lupus nephritis patients produce antibodies to a second 60 kDa red cell protein which is distinct from the Ro/SSA protein and which we have designated "N" for nephritogen. The goal of this proposal is to fully characterize the red cell 60 kDa Ro/SSA and red cell 50 kDa "N" proteins on the molecular level and to relate the presence of their specific antibodies with genetic factors and the occurrence of nephritis.