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 vive. Binding to this antigen is DNase sensitive which suggests that DNA or a DNA-containing molecule is being recognized.
| Original language | English |
|---|---|
| Pages (from-to) | 1748-1760 |
| Number of pages | 13 |
| Journal | Journal of Clinical Investigation |
| Volume | 97 |
| Issue number | 7 |
| State | Published - Apr 1 1996 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Medicine(all)
Cite this
Ligand recognition by murine anti-DNA autoantibodies : II. Genetic analysis and pathogenicity. / Swanson, Patrick; Yung, Raymond L.; Blatt, Neal B.; Eagan, Melissa A.; Norris, Jennifer M.; Richardson, Bruce C.; Johnson, Kent J.; Glick, Gary D.
In: Journal of Clinical Investigation, Vol. 97, No. 7, 01.04.1996, p. 1748-1760.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ligand recognition by murine anti-DNA autoantibodies
T2 - II. Genetic analysis and pathogenicity
AU - Swanson, Patrick
AU - Yung, Raymond L.
AU - Blatt, Neal B.
AU - Eagan, Melissa A.
AU - Norris, Jennifer M.
AU - Richardson, Bruce C.
AU - Johnson, Kent J.
AU - Glick, Gary D.
PY - 1996/4/1
Y1 - 1996/4/1
N2 - 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 vive. Binding to this antigen is DNase sensitive which suggests that DNA or a DNA-containing molecule is being recognized.
AB - 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 vive. Binding to this antigen is DNase sensitive which suggests that DNA or a DNA-containing molecule is being recognized.
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M3 - Article
VL - 97
SP - 1748
EP - 1760
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 7
ER -