Anti-DNA antibody derived from a systemic lupus erythematosus (SLE) patient forms histone–DNA–anti-DNA complexes that bind to rat glomeruli in vivo

摘要

Histone can mediate the binding of both free DNA and DNA complexed to anti-DNA antibody to the glomerular capillary wall. We tested whether preformed histone–DNA–anti-DNA immune complexes (IC) could bind to the glomerular capillary wall. The immune complex, generated with anti-DNA antibody derived from an SLE patient and excess of 125I-DNA followed by digestion with DNase, was mixed with histones. The complex containing 4 μg DNA was injected via the aorta into the left kidney of rats. At 15 min, 1.3% of the histone–DNA–anti-DNA antibody complex bound (measured as 125I-DNA), when histone was omitted less than 0.1% of the DNA–anti-DNA antibody complex bound. By immunofluorescence human immunoglobulins and histones, representing the IC, could be observed in a capillary pattern; but no complement deposition was detected. Electron microscopy revealed discrete, electron dense deposits in a subendothelial, subepithelial and mesangial localization at 15 min. These results provide direct evidence that antibodies from serum of SLE patients can form soluble histone–DNA–anti-DNA immune complexes that bind to the glomerular capillary wall in vivo