Plasma dna in systemic lupus erythematosus. Characterization of cloned base sequences

Abstract

Little is known about plasma DNA in patients with systemic lupus erythematosus (SLE). Previous studies have suggested that it may, in fact, not be derived from the random nucleolysis that might be expected to accompany cell death, which might have been the simplest explanation of its origin. To extend the results of other studies, plasma DNA, obtained from a subgroup of SLE patients who had large amounts of immunoprecipitable plasma DNA, was cloned into a plasmid vector, and the nucleotide base sequences were studied by nucleic acid hybridization. One possible explanation for the anomalous renaturation kinetics of plasma DNA in SLE--namely, that it contained non-human genomic base sequences--was rendered untenable by the fact that 51 consecutive DNA clones from 2 SLE patients were each shown to contain human genomic DNA sequences. Plasma DNA from SLE patients also differed from human genomic control DNA in that those sequences derived from the highly repetitive fraction of human DNA were specifically enriched in one such sequence, Alu, which constituted 55% of the repeat sequences in the plasma DNA clones as compared with 13% in control DNA clones. There was a decrease in the frequency of non-Alu repeat sequences (9% for plasma DNA compared with 23% in control DNA). These differences were statistically significant, and they indicate that SLE plasma DNA contains a nonrandom selection of human genomic base sequences. Several explanations for these findings are considered.