The complement mediated binding of prepared antib~dy/~H-dsDNA immune complexes to the red blood cells obtained from a number of patient populations has been investigated. Patients with solid tumors have binding activity similar to that seen in a normal group of individuals. However, a significant fraction of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies have lowered binding activity compared with normal subjects. Quantitative studies indicate the lowered activity probably arises due to a decrease in complement receptors on the respective red blood cells. The potential importance and implications of these findings are briefly discussed. It is well established that complement-fixing antibody/dsDNA immune complexes play a key role in the pathogenesis of SLE (17,18). We have previously performed quantitative experiments (5-8) which demonstrate that large, soluble antibody/dsDNA immune complexes bind to the CR, receptors of normal human

No abstract

The kinetics of binding of prepared complement opsonized 3H‐dsDNA/anti‐DNA immune complexes to normal red blood cells (RBCs) and to RBCs with lowered immune complex binding capacity from certain patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis was examined. Normal RBCs bound the immune complexes rapidly and reached equilibrium in about 4 minutes at 37°C, while the SLE RBCs not only bound less immune complex but required up to 30 minutes to reach equilibrium. Chemical modification of normal RBCs with moderate amounts of dithiothreitol, an agent that destroys the binding activity of the C3b receptor (CR1), produced RBCs that mimicked the equilibrium and kinetic binding properties of the SLE RBCs. These observations, taken in conjunction with a detailed examination of the temperature dependence of the binding kinetics, suggest that CR1 reorganization on the RBC surface to form binding clusters may be an essential step in the complement mediated binding of immune complexes to RBCs. The implications of these findings with respect to the clearance of immune complexes from the circulation of patients with autoimmune diseases are discussed.

In vivo binding of double‐stranded DNA (dsDNA) to renal glomeruli of rats was examined. 125I‐dsDNA (600 basepairs) was perfused with 131I‐IgG as a blood marker into the right renal artery of normal rats, and blood flow was restored. After 10 minutes, isolated glomeruli showed a specific uptake of DNA, which increased in a saturable fashion with increasing doses of administered DNA. To exclude the possibility that 125I in the glomeruli represented only DNA breakdown products, we extracted the DNA from the glomeruli for analysis by polyacrylamide gel electrophoresis. The extracted DNA was 120–200 bp in size, which is large enough to bind antibodies to DNA. In contrast, the radioactivity of DNA taken up by the liver or renal tissues other than glomeruli was predominantly tri‐chloroacetic acid soluble, i.e., <15 bp. Immunofluorescence studies showed that antibodies to DNA, administered after DNA, were present in glomeruli. Our data indicate that dsDNA binds to glomeruli in vivo in a saturable manner, and remains large enough to be antigenic. Therefore, the binding of DNA to glomeruli, followed by interaction with antibodies to dsDNA may be a mechanism for DNA–anti‐DNA complex formation in glomeruli in patients with systemic lupus erythematosus.

No abstract