DNA sequence and conformation specificity of lupus autoantibodies. Preferential binding to the left-handed Z-DNA form of synthetic polynucleotides.
The binding specificity of 16 sera from systemic lupus erythematosus (SLE) patients was studied by enzyme-linked immunosorbent assay (ELISA), using 4 native DNAs of different guanine-cytosine (G-C) content and a group of synthetic polynucleotides. All the SLE sera showed increased binding to poly(dA-dC).poly(dG-dT), compared with calf thymus DNA in the right-handed B conformation. No significant differences were noted in binding of selected SLE sera to the native DNAs that differed in G-C content or superhelicity of DNA. With poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG-m5dC), the majority of SLE sera showed a preferential binding to the salt-induced Z form, compared with the B form. In addition, an average twelve-fold increase was found in binding to Z-form brominated poly(dG-dC).poly(dG-dC) compared with B-form poly(dG-dC).poly(dG-dC), when the polymers were coated on the plates in 0.15M NaCl. The preferential binding of SLE sera to poly(dA-dC).poly(dG-dT) and to Z-DNA may be important in the formation of circulating immune complexes and subsequent vascular damage, or may provide a clue to the mechanism of production of anti-DNA antibodies in this disease.
Thomas
T J
TJ
Department of Medicine, University of Minnesota School of Medicine, Minneapolis.
Meryhew
N L
NL
Messner
R P
RP
D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D001666:Binding Sites, Antibody; D004247:DNA / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008968:Molecular Conformation; D011119:Polynucleotides / Q000138:chemical synthesis / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D011119:Polynucleotides; D004247:DNA