Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1987 Oct 1;166(4):850–863. doi: 10.1084/jem.166.4.850

DNA receptor dysfunction in systemic lupus erythematosus and kindred disorders. Induction by anti-DNA antibodies, antihistone antibodies, and antireceptor antibodies

PMCID: PMC2188722  PMID: 2821153

Abstract

The ability of sera from patients with SLE and similar connective tissue diseases to induce dysfunction of the receptor for DNA was studied. All SLE and MCTD sera studied resulted in marked inhibition of DNA receptor binding. Furthermore, the sera from a subgroup of patients with other rheumatic diseases and a surprisingly high percentage of asymptomatic relatives of SLE patients exhibited a similar effect. The humoral factors causing this defect were shown to be of at least three reactivities: (a) antibodies to DNA, (b) antibodies to histones, and (c) antibodies to the DNA receptor itself. The reactivity of anti-DNA and antihistone antibodies is dependent upon intact cell-surface DNA, and reconstitution experiments suggest that antihistone antibodies are reactive with histones complexed to this DNA, which in turn is bound to the DNA receptor. Cells with an antibody-induced DNA receptor defect are unable to bind DNA; the subsequent inability to degrade DNA may have important consequences in diseases such as SLE in which DNA-anti- DNA immune complexes are of pathogenetic significance.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Abdou N. I., Wall H., Lindsley H. B., Halsey J. F., Suzuki T. Network theory in autoimmunity. In vitro suppression of serum anti-DNA antibody binding to DNA by anti-idiotypic antibody in systemic lupus erythematosus. J Clin Invest. 1981 May;67(5):1297–1304. doi: 10.1172/JCI110158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bennett R. M., Davis J., Campbell S., Portnoff S. Lactoferrin binds to cell membrane DNA. Association of surface DNA with an enriched population of B cells and monocytes. J Clin Invest. 1983 Mar;71(3):611–618. doi: 10.1172/JCI110807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bennett R. M., Davis J., Merritt M. Anti-DNA antibodies react with DNA expressed on the surface of monocytes and B lymphocytes. J Rheumatol. 1986 Aug;13(4):679–685. [PubMed] [Google Scholar]
  4. Bennett R. M., Gabor G. T., Merritt M. M. DNA binding to human leukocytes. Evidence for a receptor-mediated association, internalization, and degradation of DNA. J Clin Invest. 1985 Dec;76(6):2182–2190. doi: 10.1172/JCI112226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bennett R. M., O'Connell D. J. Mixed connective tisssue disease: a clinicopathologic study of 20 cases. Semin Arthritis Rheum. 1980 Aug;10(1):25–51. doi: 10.1016/0049-0172(80)90013-x. [DOI] [PubMed] [Google Scholar]
  6. Bennett R. M., Peller J. S., Merritt M. M. Defective DNA-receptor function in systemic lupus erythematosus and related diseases: evidence for an autoantibody influencing cell physiology. Lancet. 1986 Jan 25;1(8474):186–188. doi: 10.1016/s0140-6736(86)90656-2. [DOI] [PubMed] [Google Scholar]
  7. DeHoratius R. J., Pillarisetty R., Messner R. P., Talal N. Anti-nucleic acid antibodies in systemic lupus erythematosus patients and their families. Incidence and correlation with lymphocytotoxic antibodies. J Clin Invest. 1975 Nov;56(5):1149–1154. doi: 10.1172/JCI108190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dwyer D. S., Bradley R. J., Urquhart C. K., Kearney J. F. Naturally occurring anti-idiotypic antibodies in myasthenia gravis patients. Nature. 1983 Feb 17;301(5901):611–614. doi: 10.1038/301611a0. [DOI] [PubMed] [Google Scholar]
  9. Fox R. I., Robinson C. A., Curd J. G., Kozin F., Howell F. V. Sjögren's syndrome. Proposed criteria for classification. Arthritis Rheum. 1986 May;29(5):577–585. doi: 10.1002/art.1780290501. [DOI] [PubMed] [Google Scholar]
  10. Gabor G., Bennett R. M. Biotin-labelled DNA: a novel approach for the recognition of a DNA binding site on cell membranes. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1034–1039. doi: 10.1016/0006-291x(84)91195-1. [DOI] [PubMed] [Google Scholar]
  11. Gaulton G. N., Greene M. I. Idiotypic mimicry of biological receptors. Annu Rev Immunol. 1986;4:253–280. doi: 10.1146/annurev.iy.04.040186.001345. [DOI] [PubMed] [Google Scholar]
  12. Holers V. M., Kotzin B. L. Human peripheral blood monocytes display surface antigens recognized by monoclonal antinuclear antibodies. J Clin Invest. 1985 Sep;76(3):991–998. doi: 10.1172/JCI112100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kotzin B. L., Lafferty J. A., Portanova J. P., Rubin R. L., Tan E. M. Monoclonal anti-histone autoantibodies derived from murine models of lupus. J Immunol. 1984 Nov;133(5):2554–2559. [PubMed] [Google Scholar]
  14. LEVY H. B., SOBER H. A. A simple chromatographic method for preparation of gamma globulin. Proc Soc Exp Biol Med. 1960 Jan;103:250–252. doi: 10.3181/00379727-103-25476. [DOI] [PubMed] [Google Scholar]
  15. Manak R. C., Voss E. W., Jr Anti-sDNA antibody purified from sera of human patients with systemic lupus erythematosus--i. Purification and characterization. Immunochemistry. 1978 Sep;15(9):643–651. doi: 10.1016/0161-5890(78)90038-x. [DOI] [PubMed] [Google Scholar]
  16. Meinke W., Hall M. R., Goldstein D. A., Kohne D. E., Lerner R. A. Physical properties of cytoplasmic membrane-associated DNA. J Mol Biol. 1973 Jun 25;78(1):43–56. doi: 10.1016/0022-2836(73)90427-0. [DOI] [PubMed] [Google Scholar]
  17. Morimoto C., Reinherz E. L., Distaso J. A., Steinberg A. D., Schlossman S. F. Relationship between systemic lupus erythematosus T cell subsets, anti-T cell antibodies, and T cell functions. J Clin Invest. 1984 Mar;73(3):689–700. doi: 10.1172/JCI111261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moyer M. P. The association of DNA and RNA with membranes. Int Rev Cytol. 1979;61:1–61. doi: 10.1016/s0074-7696(08)61994-4. [DOI] [PubMed] [Google Scholar]
  19. Nasu H., Chia D. S., Taniguchi O., Barnett E. V. Characterization of anti-F(ab')2 antibodies in SLE patients. Evidence for cross-reacting auto-anti-idiotypic antibodies. Clin Immunol Immunopathol. 1982 Oct;25(1):80–90. doi: 10.1016/0090-1229(82)90167-2. [DOI] [PubMed] [Google Scholar]
  20. ROPES M. W., BENNETT G. A., COBB S., JACOX R., JESSAR R. A. 1958 Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis. 1958 Dec;9(4):175–176. [PubMed] [Google Scholar]
  21. Raptis L., Menard H. A. Quantitation and characterization of plasma DNA in normals and patients with systemic lupus erythematosus. J Clin Invest. 1980 Dec;66(6):1391–1399. doi: 10.1172/JCI109992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sege K., Peterson P. A. Use of anti-idiotypic antibodies as cell-surface receptor probes. Proc Natl Acad Sci U S A. 1978 May;75(5):2443–2447. doi: 10.1073/pnas.75.5.2443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES