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. 1988 Apr;85(7):2260–2264. doi: 10.1073/pnas.85.7.2260

Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype.

S Mendlovic 1, S Brocke 1, Y Shoenfeld 1, M Ben-Bassat 1, A Meshorer 1, R Bakimer 1, E Mozes 1
PMCID: PMC279970  PMID: 3258423

Abstract

Systemic lupus erythematosus (SLE) is considered to be the quintessential autoimmune disease. It has not been possible to induce SLE in animal models by DNA immunization or by challenge with anti-DNA antibodies. We herewith report a murine model of SLE-like disease induced by immunization of C3H.SW female mice with a common human monoclonal anti-DNA idiotype (16/6 idiotype). Following a booster injection with the 16/6 idiotype, high levels of murine anti-16/6 and anti-anti-16/6 antibodies (associated with anti-DNA activity) were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens [Sm, SS-A (Ro), and SS-B (La)], and cardiolipin were noted. The serological findings were associated with increased erythrocyte sedimentation rate, leukopenia, proteinuria, immune complex deposition in the glomerular mesangium, and sclerosis of the glomeruli. The immune complexes in the kidneys were shown to contain the 16/6 idiotype. This experimental SLE-like model may be used to elucidate the mechanisms underlying SLE.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ben Chetrit E., Dunsky E. H., Wollner S., Eilat D. In vivo clearance and tissue uptake of an anti-DNA monoclonal antibody and its complexes with DNA. Clin Exp Immunol. 1985 Apr;60(1):159–168. [PMC free article] [PubMed] [Google Scholar]
  2. Cukier R., Tron F. Monoclonal anti-DNA antibodies: an approach to studying SLE nephritis. Clin Exp Immunol. 1985 Oct;62(1):143–149. [PMC free article] [PubMed] [Google Scholar]
  3. Ebling F., Hahn B. H. Restricted subpopulations of DNA antibodies in kidneys of mice with systemic lupus. Comparison of antibodies in serum and renal eluates. Arthritis Rheum. 1980 Apr;23(4):392–403. doi: 10.1002/art.1780230402. [DOI] [PubMed] [Google Scholar]
  4. Hahn B. H., Ebling F. M. Suppression of NZB/NZW murine nephritis by administration of a syngeneic monoclonal antibody to DNA. Possible role of anti-idiotypic antibodies. J Clin Invest. 1983 Jun;71(6):1728–1736. doi: 10.1172/JCI110927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Isenberg D. A., Collins C. Detection of cross-reactive anti-DNA antibody idiotypes on renal tissue-bound immunoglobulins from lupus patients. J Clin Invest. 1985 Jul;76(1):287–294. doi: 10.1172/JCI111959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Isenberg D. A., Shoenfeld Y., Madaio M. P., Rauch J., Reichlin M., Stollar B. D., Schwartz R. S. Anti-DNA antibody idiotypes in systemic lupus erythematosus. Lancet. 1984 Aug 25;2(8400):417–422. doi: 10.1016/s0140-6736(84)92904-0. [DOI] [PubMed] [Google Scholar]
  7. Isenberg D., Dudeney C., Wojnaruska F., Bhogal B. S., Rauch J., Schattner A., Naparstek Y., Duggan D. Detection of cross reactive anti-DNA antibody idiotypes on tissue-bound immunoglobulins from skin biopsies of lupus patients. J Immunol. 1985 Jul;135(1):261–264. [PubMed] [Google Scholar]
  8. Konikoff F., Shoenfeld Y., Isenberg D. A., Barrison I., Sobe T., Theodor E., Slor H. Anti-Rnp antibodies in chronic liver diseases. Clin Exp Rheumatol. 1987 Oct-Dec;5(4):359–361. [PubMed] [Google Scholar]
  9. Madaio M. P., Hodder S., Schwartz R. S., Stollar B. D. Responsiveness of autoimmune and normal mice to nucleic acid antigens. J Immunol. 1984 Feb;132(2):872–876. [PubMed] [Google Scholar]
  10. Notman D. D., Kurata N., Tan E. M. Profiles of antinuclear antibodies in systemic rheumatic diseases. Ann Intern Med. 1975 Oct;83(4):464–469. doi: 10.7326/0003-4819-83-4-464. [DOI] [PubMed] [Google Scholar]
  11. SELA M., FUCHS S., ARNON R. Studies on the chemical basis of the antigenicity of proteins. 5. Synthesis, characterization and immunogenicity of some multichain and linear polypeptides containing tyrosine. Biochem J. 1962 Oct;85:223–235. doi: 10.1042/bj0850223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Schwartz R. S., Stollar B. D. Origins of anti-DNA autoantibodies. J Clin Invest. 1985 Feb;75(2):321–327. doi: 10.1172/JCI111704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Shoenfeld Y., Isenberg D. A., Rauch J., Madaio M. P., Stollar B. D., Schwartz R. S. Idiotypic cross-reactions of monoclonal human lupus autoantibodies. J Exp Med. 1983 Sep 1;158(3):718–730. doi: 10.1084/jem.158.3.718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Shoenfeld Y., Rauch J., Massicotte H., Datta S. K., André-Schwartz J., Stollar B. D., Schwartz R. S. Polyspecificity of monoclonal lupus autoantibodies produced by human-human hybridomas. N Engl J Med. 1983 Feb 24;308(8):414–420. doi: 10.1056/NEJM198302243080802. [DOI] [PubMed] [Google Scholar]
  15. Stocks M. R., Williams D. G., Maini R. N. Differential induction of lupus associated antinuclear antibodies in MRL mice by monoclonal anti-Sm antibodies. Clin Exp Immunol. 1987 Mar;67(3):492–499. [PMC free article] [PubMed] [Google Scholar]
  16. Theofilopoulos A. N., Dixon F. J. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269–390. doi: 10.1016/s0065-2776(08)60342-9. [DOI] [PubMed] [Google Scholar]
  17. Yamagata H., Harley J. B., Reichlin M. Molecular properties of the Ro/SSA antigen and enzyme-linked immunosorbent assay for quantitation of antibody. J Clin Invest. 1984 Aug;74(2):625–633. doi: 10.1172/JCI111460. [DOI] [PMC free article] [PubMed] [Google Scholar]

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