Reaction of antipolynucleotide antibody from systemic lupus erythematosus patient serum with double‐stranded DNA complexed to protein

Abstract

Antipolynucleotide antibody from systemic lupus erythematosus patient serum was found'to interact with common determinants of double-stranded DNA (dsDNA) complexed to protein within nucleosomes, and with protein-free denatured DNA. In contrast, purified dsDNA isolated from nucleosomes manifested decreased reactivity with antipolynucleotide antibody. These data suggest that immunoassays using denatured DNA antigen substrate are useful for identifying a broad spectrum of antipolynucleotide antibodies that are reactive with dsDNA complexed to protein.The presence of high-avidity antibody that is reactive with double-stranded DNA (dsDNA) is one of the major diagnostic criteria for systemic lupus erythematosus (SLE) (1). Increased titers of this antibody have also been closely correlated with flares of disease activity (2). Protein-free dsDNA is used as the antigen substrate in most immunoassays that detect or quantitate this antibody. However, in vivo, dsDNA exists as a complex with proteins, such as histone. Inasmuch as local protein-DNA interaction has been shown to alter helical conformation (3-9, one would expect differences in the reaction of antipolynucleotide antibody from SLE serum with purified dsDNA

Genesis and evolution of antichromatin autoantibodies in murine lupus implicates T-dependent immunization with self antigen.

“…0.1 sg/ml of P4D2, an IgG2b that (27) and antibodies crossreactive with ssDNA and chromatin have been reported (28). However, in five sera without anti-dsDNA antibodies, adsorption with chromatin in solution could only remove 4%±7% ofthe ssDNA reactive antibodies.…”