The specificities of anti-polynucleotide antibodies found in human sera were studied using several immunological procedures. Anti-native DNA (NDNA) antibodies and certain anti-double-stranded RNA (DSRNA) antibodies were found to react with single-stranded DNA (SDNA), and anti-NDNA antibodies were observed to react more avidly with SDNA than with NDNA in most sera tested. Antibodies to NDNA showed no preferential reactivity with NDNA or SDNA derived from mammalian tissue, bacterial, or viral sources. Precipitating antibodies reactive with individual bases, with common determinants of bases, and with common determinants of SDNA and NDNA were detected utilizing synthetic polydeoxyribonucleotides. Antibodies to DSRNA were also heterogeneous and reactive with both Poly A · Poly U and Poly I · Poly C in addition to reactivity with Poly A and SDNA. In contrast, antibodies to a ribonucleo-protein determined by hemagglutination and by precipitation showed no reaction with NDNA, SDNA, or DSRNA. Serial studies of serum specimens from patients with systemic lupus erythematosus (SLE) indicated that anti-NDNA antibodies were closely associated with disease activity. Titers of antibodies to SDNA or DSRNA were also frequently increased during these periods but in addition showed peaks during quiescent periods. Anti-NDNA antibodies were detected in most patients' sera at sometime during the course of the disease. Three patients were observed with active SLE, who did not develop anti-NDNA antibodies, even in the presence of severe renal disease. Evidence that other antigen-antibody systems may also play a role in the pathogenesis of the renal disease was particularly apparent in these patients. Anti-ribonucleoprotein antibodies were not well correlated with the peaks of antibody activity of other polynucleotide antibodies, suggesting that an independent immunogen was responsible for induction of these antibodies. The close association of certain populations of anti-polynucleotide antibodies during the course of active SLE, the presence of cross-reacting antigenic determinants of SDNA, NDNA, and DSRNA, the preferential avidity of anti-NDNA antibodies for SDNA, and the frequent increase of anti-SDNA antibodies in SLE and other diseases associated with active tissue destruction suggest that SDNA is a ubiquitous antigen that may stimulate the formation of antibodies reactive with a variety of polynucleotides.

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Serological studies, immunofluorescence studies, and immunochemical assays of glomerular eluates indicate that several antigen-antibody systems may be involved in the pathogenesis of the tissue lesions of SLE. The NDNA-anti-NDNA system appears to be operative in most patients with active SLE. In addition, antibodies to SDNA are found with considerable frequency in SLE sera and glomerular eluates. It is not known if these antibodies fix to NDNA which has been denatured after deposition in glomeruli or if SDNA-anti-DNA complexes are deposited initially. NDNA antigen has been demonstrated in both serum and glomerular deposits, and SDNA determinants have also been found in glomerular deposits. In addition, there is evidence that rheumatoid factor contributes to the immune complex deposition in certain patients either by fixing to preformed immune complexes or as part of an independent γ-globulin-anti-γ-globulin system. It is anticipated that the definition of these immune systems, and the assessment of their relative toxicity will provide insight into underlying etiologic factors as well as provide a sound basis for therapy in this form of glomerulonephritis.