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...

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Bibliographic Details
Published in:Arthritis and rheumatism 1988-03, Vol.31 (3), p.367-377
Main Authors: Thomas, T. J., Meryhew, Nancy L., Messner, Ronald P.
Format: Article
Language:English
Subjects:
Antibody Specificity
Autoantibodies - genetics
Autoantibodies - immunology
Autoantibodies - metabolism
Base Sequence
Binding Sites, Antibody
Biological and medical sciences
DNA - genetics
DNA - immunology
Humans
Lupus Erythematosus, Systemic - immunology
Medical sciences
Molecular Conformation
Polynucleotides - chemical synthesis
Polynucleotides - immunology
Polynucleotides - metabolism
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
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Summary: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.
ISSN:0004-3591
1529-0131
DOI:10.1002/art.1780310308