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Research Article Free access | 10.1172/JCI118602

Ligand recognition by murine anti-DNA autoantibodies. II. Genetic analysis and pathogenicity.

P C Swanson, R L Yung, N B Blatt, M A Eagan, J M Norris, B C Richardson, K J Johnson, and G D Glick

Department of Chemistry, University of Michigan, Ann Arbor, 48109-1055, USA.

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Department of Chemistry, University of Michigan, Ann Arbor, 48109-1055, USA.

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Department of Chemistry, University of Michigan, Ann Arbor, 48109-1055, USA.

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Department of Chemistry, University of Michigan, Ann Arbor, 48109-1055, USA.

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Department of Chemistry, University of Michigan, Ann Arbor, 48109-1055, USA.

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Department of Chemistry, University of Michigan, Ann Arbor, 48109-1055, USA.

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Department of Chemistry, University of Michigan, Ann Arbor, 48109-1055, USA.

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Department of Chemistry, University of Michigan, Ann Arbor, 48109-1055, USA.

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Published April 1, 1996 - More info

Published in Volume 97, Issue 7 on April 1, 1996
J Clin Invest. 1996;97(7):1748–1760. https://doi.org/10.1172/JCI118602.
© 1996 The American Society for Clinical Investigation
Published April 1, 1996 - Version history
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Abstract

Although anti-DNA autoantibodies are an important hallmark of lupus, the relationships among anti-DNA structure, reactivity, and pathogenicity have not been fully elucidated. To further investigate these relationships, we compare the variable genes and primary structure of eight anti-DNA mAbs previously obtained from an MRL/MpJ-lpr/lpr mouse along with the ability of three representative mAbs to induce nephritis in nonautoimmune mice using established adoptive transfer protocols. One monospecific anti-single-stranded (ss) DNA (11F8) induces severe diffuse proliferative glomerulonephritis in nonautoimmune mice whereas another anti-ssDNA with apparently similar in vitro binding properties (9F11) and an anti-double-stranded DNA (4B2) are essentially benign. These results establish a murine model of anti-DNA-induced glomerular injury resembling the severe nephritis seen in lupus patients and provide direct evidence that anti-ssDNA can be more pathogenic than anti-double-stranded DNA. In vitro binding experiments using both protein-DNA complexes and naive kidney tissue indicate that glomerular localization of 11F8 may occur by recognition of a planted antigen in vivo. Binding to this antigen is DNase sensitive which suggests that DNA or a DNA-containing molecule is being recognized.

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