Folded DNA Fragments Explain Why Lupus Antibodies Bind Denatured DNA

Stollar and Papalian, writing in The Journal of Clinical Investigation in 1980, found that antibodies from people with systemic lupus erythematosus (SLE), an autoimmune disease, react with denatured (single-stranded) DNA mainly because parts of that DNA fold back into stable double-stranded, helix-like regions rather than staying fully unwound.

The researchers worked with purified DNA and SLE patient blood serum in laboratory binding assays, not with animals or patients directly. They used an enzyme called S1 nuclease, which cuts single-stranded DNA, to strip away unstructured regions and isolate resistant "cores" of 20 to several hundred base pairs. These cores still had helical structure and still competed with native (double-stranded) DNA for binding by SLE antibodies. Heating the DNA, which disrupts folded structure, reduced its ability to compete, while native DNA's binding was unaffected by the same temperature range. Tests with single DNA building blocks, short DNA chains, repetitive DNA polymers, and RNA-DNA hybrids showed that two strands of polydeoxyribonucleotide — DNA's chemical backbone — needed to pair up for the antibodies to bind well.

As a laboratory biochemistry study, the paper cannot say how this process unfolds in living patients or how it relates to disease symptoms; it identifies a structural mechanism, not a clinical outcome.