Ligand recognition by murine anti-DNA autoantibodies

II. Genetic analysis and pathogenicity

Patrick Swanson, Raymond L. Yung, Neal B. Blatt, Melissa A. Eagan, Jennifer M. Norris, Bruce C. Richardson, Kent J. Johnson, Gary D. Glick

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 languageEnglish
Pages (from-to)1748-1760
Number of pages13
JournalJournal of Clinical Investigation
Volume97
Issue number7
StatePublished - Apr 1 1996
Externally publishedYes

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Autoantibodies
Virulence
Ligands
DNA
Nephritis
Antigens
Deoxyribonucleases
Adoptive Transfer
Single-Stranded DNA
Glomerulonephritis
Kidney
Wounds and Injuries
Genes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Swanson, P., Yung, R. L., Blatt, N. B., Eagan, M. A., Norris, J. M., Richardson, B. C., ... Glick, G. D. (1996). Ligand recognition by murine anti-DNA autoantibodies: II. Genetic analysis and pathogenicity. Journal of Clinical Investigation, 97(7), 1748-1760.

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 journalArticle

Swanson, P, Yung, RL, Blatt, NB, Eagan, MA, Norris, JM, Richardson, BC, Johnson, KJ & Glick, GD 1996, 'Ligand recognition by murine anti-DNA autoantibodies: II. Genetic analysis and pathogenicity', Journal of Clinical Investigation, vol. 97, no. 7, pp. 1748-1760.
Swanson P, Yung RL, Blatt NB, Eagan MA, Norris JM, Richardson BC et al. Ligand recognition by murine anti-DNA autoantibodies: II. Genetic analysis and pathogenicity. Journal of Clinical Investigation. 1996 Apr 1;97(7):1748-1760.
Swanson, Patrick ; Yung, Raymond L. ; Blatt, Neal B. ; Eagan, Melissa A. ; Norris, Jennifer M. ; Richardson, Bruce C. ; Johnson, Kent J. ; Glick, Gary D. / Ligand recognition by murine anti-DNA autoantibodies : II. Genetic analysis and pathogenicity. In: Journal of Clinical Investigation. 1996 ; Vol. 97, No. 7. pp. 1748-1760.
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