Antibodies to Polynucleotides in Human Sera: Antigenic Specificity and Relation to Disease

Abstract

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.

Serum levels of C1q, C1r and C1s in normal and pathologic sera

“…Low levels of Clq, C3 and been reported repeatedly in which immune complexes are CH,, have diseases in thought to play an important role (24). Complement fixation by immune complexes follows primarily the classic pathway of C activation with the generation of CT (C1 esterase) and CZ2 (C3 convertase) and the activation of late components (10).…”

Clinical Significance of Anti–double‐stranded Dna Antibodies Detected by a Solid Phase Enzyme Immunoassay

“…It is strongly anionic, manifesting nonimmunologic interactions which may interfere with antibody binding (4). The anti-dsDNA antibody population is heterogeneous with respect to class (5-7), complement fixing properties (8,9), avidity (10-16), and specificity (17,18). The concurrence of antibodies to single-stranded DNA (19), frequently in high titer, in sera of patients with SLE may be responsible for false positive or spuriously elevated titers of anti-dsDNA antibodies unless the conditions of the assay maintain the double-stranded structure of DNA (20).…”

Anti‐DNA antibody in procainmide‐induced lupus erythematosus. Determination using DNA fractionated by methylated albumin‐kieselguhr chromatography

“…Anti-dDNA is often found (3,22), but its relationship to the clinical manifestations have not been established. Data concerning the presence of anti-nDNA are conflicting (3,13,22,27).…”

“…T h e clinical significance of anti-nDNA in these non-SLE conditions is unknown. Anti-dDNA, on the other hand, occurs rather ubiquitously (3,9), but its relationship to clinical activity in disease other than SLE is also conjectural (14).…”