Advertisement

Antibodies to DNA Epiphenomena or Pathogens?

  • Bevra H. Hahn

Abstract

The study of antibodies directed against DNA began in the 1950s with the discovery of the L.E. cell by Hargraves. Several investigators found that the L.E. cell phenomenon resulted from ingestion of altered nuclear material by circulating phagocytic cells. Close examination of that material showed that it consisted of DNA-protein (predominantly DNA-histone) and IgG. Thus, the existence of antibodies to the supposedly “forbidden” constituents of the human nucleus was recognized.

Keywords

Systemic Lupus Erythematosus Systemic Lupus Erythematosus Patient Lupus Nephritis Glomerular Basement Membrane Active Systemic Lupus Erythematosus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abdou, N. I., Wall, H., Lindsley, H. B., Halsey, J. F., and Suzuki, T., 1981, Network theory in autoimmunity. In vitro suppression of serum anti-DNA antibody binding to DNA by anti-idiotypic antibody in SLE, J. Clin. Invest. 67: 1297–1304.PubMedCrossRefGoogle Scholar
  2. Adams, R. L. P. (ed.), 1976, Davidson’s The Biochemistry of the Nucleic Acids, Academic Press, New York.Google Scholar
  3. Alarcon-Segovia, D., 1975, Drug induced systemic lupus erythematosus and related syndromes, Clin. Rheum. Dis. 1: 573–592.Google Scholar
  4. Andrezejewski, C., Jr., Stollar, B. D., Lalor, T. M., and Schwartz, R. S., 1980, Hybridoma auto-antibodies to DNA, J. Immunol. 124: 1499–1503.Google Scholar
  5. Arana, R., and Seligmann, M., 1967, Antibodies to native and denatured deoxyribonucleic acid in SLE, J. Clin. Invest. 46: 1867–1882.PubMedCrossRefGoogle Scholar
  6. Arnett, F. C., Jr., 1983, Systemic lupus erythematosus: Current state of the genetic hypothesis, in: Current Topics in Rheumatology ( B. H. Hahn, F. C. Arnett, T. M. Zizic, and M. C. Hochberg, eds.), The Upjohn Co., Kalamazoo, MI, pp. 1–160.Google Scholar
  7. Bankhurst, A. D., Williams, R. D., Jr., 1975, Identification of DNA-binding lymphocytes in patients with SLE, J. Clin. Invest. 56: 1378–1385.PubMedCrossRefGoogle Scholar
  8. Blomgren, S. E., Condemi, J. J., and Vaughan, J. H., 1972, Procainamide induced lupus. Clinical and laboratory manifestations, Am. J. Med. 52: 338–348.PubMedCrossRefGoogle Scholar
  9. Border, W. A., Ward, H. J., Kamil, E. S., and Cohen, A. H., 1982, Induction of membranous nephropathy in rabbits by administration of cationic antigen, J. Clin. Invest. 69: 451–456.PubMedCrossRefGoogle Scholar
  10. Borel, Y., Lewis, R. M., Andre-Schwartz, J., Stollar, B. D., and Deinen, L., 1978, Treatment of lupus nephritis in adult (NZB x NZW) Fi mice by cortisone-facilitated tolerance to nucleic acid antigens, J. Clin. Invest. 61: 276–286.PubMedCrossRefGoogle Scholar
  11. Ceppellini, R., Polli, E., and Celada, F., 1957, A DNA reacting factor in serum of a patient with lupus erythematosus diffusus, Proc. Soc. Exp. Biol. Med. 96: 572–575.PubMedGoogle Scholar
  12. Creighton, W. D., Katz, D. H., and Dixon, F. J., 1979, Antigen-specific immunocompetency, B cell function, and regulatory helper and suppressor T cell activities in spontaneously autoimmune mice, J. Immunol. 123: 2627–2636.PubMedGoogle Scholar
  13. Dang, H., and Harbeck, R. J., 1984, The in vivo and In vitro glomerular deposition of isolated anti-double- stranded-DNA antibodies in NZBAV mice, Clin. Immunol. Immunopathol. 30: 265–270.PubMedCrossRefGoogle Scholar
  14. Datta, S. K., Stollar, B. D., and Schwartz, R. S., 1983, Normal mice express idiotypes related to autoantibody idiotypes of lupus mice, Proc. Natl. Acad. Sci. U.S.A. 80: 2723–2727.PubMedCrossRefGoogle Scholar
  15. Dixon, F. J., 1982, Murine lupus—an overview, Arthritis Rheum. 25: 721–725.PubMedCrossRefGoogle Scholar
  16. Ebling, F. M., and Hahn, B. H., 1980, Restricted subpopulations of DNA antibodies in kidneys of mice with SLE, Arthritis Rheum. 23: 392–403.PubMedCrossRefGoogle Scholar
  17. Eschar, Z., Benecerraf, B., and Katz, D. H., 1975, Induction of tolerance to nucleic acid determinants by administration of a complex of nucleoside D-glutamic acid and D-lysine (D-GL), J. Immunol. 114: 872–876.Google Scholar
  18. Fischbach, M., Rabbie, J., and Talal, N., 1981, Comparison of different antinucleic acid antibody spectrotypes in spontaneous, induced and murine lupus, J. Clin. Invest. 68: 1036–1043.PubMedCrossRefGoogle Scholar
  19. Fong, S., Gilbertson, T. A., and Carson, D. A., 1983, The internal image of IgG in cross-reactive anti-idiotype antibodies against human rheumatoid factors, J. Immunol. 131: 719–724.PubMedGoogle Scholar
  20. Frank, M. M., Hamburger, M. I., Lawley, T. J., Kimberly, R. P., and Plotz, P. H., 1979, Defective reticuloendothelial system Fc-receptor function in SLE, N. Engl. J. Med. 300: 518–523.PubMedCrossRefGoogle Scholar
  21. Fries, J. F., and Holman, H. R., 1975, Systemic Lupus Erythematosus: A Clinical Analysis, W. B. Saunders, Philadelphia.Google Scholar
  22. Gallo, G. R., Caulin-Glaser, T., and Lamm, M. E., 1981, Charge of circulating immune complexes as a factor in glomerular basement membrane localization in mice, J. Clin. Invest. 67: 1305–1313.PubMedCrossRefGoogle Scholar
  23. Gershwin, E. M., and Steinberg, A. D., 1974, Qualitative characteristics of anti-DNA antibodies in lupus nephritis, Arthritis Rheum. 17: 947–954.PubMedCrossRefGoogle Scholar
  24. Golan, D. T., and Borel, Y., 1983, Spontaneous increase of DNA turnover in murine SLE, Eur. J. Immunol. 13: 430–433.PubMedCrossRefGoogle Scholar
  25. Haakenstad, A. O., and Mannik, M., 1974, Saturation of the reticuloendothelial system with soluble immune complexes, J. Immunol. 112: 1939–1948.PubMedGoogle Scholar
  26. Hahn, B. H., and Ebling, F. M., 1983, Suppression of NZB/NZW murine nephritis by administration of syngeneic monoclonal antibody to DNA. Possible role of anti-idiotypic antibodies, J. Clin. Invest. 71: 1728–1736.PubMedCrossRefGoogle Scholar
  27. Hahn, B. H., and Ebling, F. M., 1984, Suppression of murine lupus nephritis by administration of an anti- idiotypic antibody to anti-DNA, J. Immunol. 132: 187–190.PubMedGoogle Scholar
  28. Hahn, B. H., and Ebling, F. M., 1984, Similar public idiotype determinants are present on cationic IgG antibodies to DNA in mice of unrelated lupus-prone strains, J. Immunol. 133: 3015–3019.PubMedGoogle Scholar
  29. Hahn, B. H., Sharp, G. C., Irvin, W. S., Kantor, O. S., Gardner, C. A., Bagby, M., Perry, H. M., Jr., and Osterland, C. K., 1972, Immune responses to hydralazine and nuclear antigens in hydralazine-induced lupus erythematosus, Am. J. Med. 76: 365–374.Google Scholar
  30. Izui, J., Lambert, P.-H., and Miescher, P. A., 1976, In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA, J. Exp. Med. 144: 428–443.Google Scholar
  31. Izui, S., Zaldivar, N., Scher, I., and Lambert, P. H., 1977, Mechanisms for induction of anti-DNA antibodies by bacterial lipopolysaccharide in mice, J. Immunol. 119: 2151–2154.PubMedGoogle Scholar
  32. Jarros, E. M., Gjaravo, N. E., and Hughes, G. R. V., 1983, Cardiolipin antibodies: Detection by radioimmunoassay and association with thrombosis in SLE, Lancet 2: 1211–1214.Google Scholar
  33. Jerne, N. K., 1971, Towards a network theory of the immune system, Ann. Immunol. 125C: 373–377.Google Scholar
  34. Johnson, G. E., Edmonds, J. P., and Holborow, E. J., 1973, Precipitating antibodies to DNA detected by two-stage electroimmunodiffusion: Studies in SLE and in RA, Lancet 2: 883–885.PubMedCrossRefGoogle Scholar
  35. Koffler, D., Carr, R., Agnello, V., Thoburn, R., and Kunkel, H. G., 1971, Antibodies to polynucleotides in human sera: Antigenic specificity and relation to disease, J. Exp. Med. 134: 294–312.PubMedCrossRefGoogle Scholar
  36. Lafer, E. M., Rauch, J., Andrezejewski, C., Jr., Mudd, D., Furic, B., Schwartz, R. S., and Stollar, B. D., 1981, Poly specific monoclonal lupus antibodies reactive with both polynucleotides and phospholipids, J. Exp. Med. 153: 897–909.PubMedCrossRefGoogle Scholar
  37. Lafer, E. M., Valle, R. P. C., Moller, A., Nordheim, A., Schur, P. H., Rich, A., and Stollar, B. D., 1983, Z-DNA-specific antibodies in human SLE, J. Clin. Invest. 71: 314–320.PubMedCrossRefGoogle Scholar
  38. Lahita, R. G., Bradlow, H. L., Kunkel, H. G., and Fishman, J., 1981, Increased 16-hydroxylation of estradiol in SLE, J. Clin. Endocrinol. Metab. 53: 174–178.PubMedCrossRefGoogle Scholar
  39. Lambert, P. H., and Dixon, F. J., 1968, Pathogenesis of glomerulonephritis of NZB/W mice, J. Exp. Med. 127: 507–522.PubMedCrossRefGoogle Scholar
  40. Laskin, C. A., Taurog, J. D., Smathers, P. A., and Steinberg, A. D., 1981, Studies of defective tolerance in murine lupus, J. Immunol. 127: 1743–1747.PubMedGoogle Scholar
  41. Magilavy, D. B., Hundley, T. R., Steinberg, A. D., and Finbloom, D. S., 1983, Abnormal binding of soluble IgG immune complexes to hepatic nonparenchymal cells of autoimmune mice, J. Immunol. 131: 2784–2788.PubMedGoogle Scholar
  42. Marion, T. N., Lawton, A. R. Ill, Kearney, J. F., and Briles, D. E., 1982, Anti-DNA autoantibody in (NZB x ZW) Fi, mice are clonally heterogeneous, but the majority share a common idiotype, J. Immunol. 128: 668–671.PubMedGoogle Scholar
  43. Munns, T. W., Liszewski, M. K., Tellam, J. T., Ebling, F. M., and Hahn, B. H., 1982, Antibody mucleic acid complexes. Indentification of the antigenic determinant of a murine monoclonal antibody specific for single-stranded nucleic acids, Biochemistry 21: 2929–2939.PubMedCrossRefGoogle Scholar
  44. Munns, T. W., Liszewski, M. K., and Hahn, B. H., 1984, Antibody nucleic acid complexes. Conformational and base specificities associated with spontaneously-occurring poly-acid monoclonal anti-DNA antibodies from autoimmune mice, Biochemistry 23: 2964–2970.PubMedCrossRefGoogle Scholar
  45. Nasa, H., Chia, D. S., Taniguchi, O., and Barnett, E. V., 1982, Characterization of antiF(ab’)2 antibodies in SLE patients, Clin. Immunol. Immunopathol. 25: 80–84.CrossRefGoogle Scholar
  46. Papalian, M., Lafer, E., Wong, R., and Stollar, B. D., 1980, Reaction of SLE anti-native DNA antibodies with native DNA fragments from 20 to 1200 base pairs, J. Clin. Invest. 65: 469–477.PubMedCrossRefGoogle Scholar
  47. Parker, L. P., Hahn, B. H., and Osterland, C. K., 1974, Modification of NZB/NZW Fi autoimmune disease by development of tolerance to DNA, J. Immunol. 113: 292–312.PubMedGoogle Scholar
  48. Pearson, L., and Lightfoot, R. W., Jr., 1981, Correlation of DNA-anti-DNA association rates with clinical activity in SLE, J. Immunol. 126: 16–19.PubMedGoogle Scholar
  49. Raptis, L., and Menard, H. A., 1980, Quantitation and characterization of plasma DNA in normals and patients with SLE, J. Clin. Invest. 66: 1391–1399.PubMedCrossRefGoogle Scholar
  50. Rauch, J., Murphy, E., Roths, J. B., Stollar, B. D., and Schwartz, R. S., 1982, A high frequency idiotypic marker of anti-DNA antibodies in MRL/lpr/lpr mice, J. Immunol. 129: 236–241.PubMedGoogle Scholar
  51. Raveche, E. S., Novotny, E. A., Hansen, C. T., Tjio, J. H., and Steinberg, A. D., 1983, Genetic studies in NZB mice. V. Recombinant inbred lines demonstrate that separate genes control autoimmune phenomena, J. Exp. Med. 153: 1187–1197.CrossRefGoogle Scholar
  52. Robbins, W. C., Holman, J. R., Diecher, H., and Kunkel, H. G., 1957, Complement fixation with cell nuclei and DNA in lupus erythematosus, Proc. Soc. Exp. Biol. Med. 96: 575–579.PubMedGoogle Scholar
  53. Rothfield, N. F., and Stollar, B. D., 1967, The relation of immunoglobulin class, pattern of antinuclear antibody, and complement-fixing antibodies to DNA in sera from patients with SLE, J. Clin. Invest. 46: 1785–1794.PubMedCrossRefGoogle Scholar
  54. Roths, J. B., 1979, in: Genetic Control of Autoimmune Disease (N. R. Rose, P. E. Bigazzi, and N. L. Warner, eds.), Elsevier/North-Holland, New York, pp. 207–217.Google Scholar
  55. Roubinian, J. R., Talal, N., Greenspan, J. S., Goodman, J. R., and Siiteri, P. K., 1978, Effect of castration and sex hormone treatment on survival, anti-nucleic-acid antibodies and glomerulonephritis in NZB/NZW F1 mice, J. Exp. Med. 147: 1568–1583.PubMedCrossRefGoogle Scholar
  56. Roubinian, J. R., Talal, N., Greenspan, J. S., Goodman, J. R., and Siiteri, P. K., 1979, Delayed androgen treatment prolongs survival in murine lupus, J. Clin. Invest. 63: 902–911.PubMedCrossRefGoogle Scholar
  57. Sano, H., Imokawa, M., Steinberg, A. D., and Morimoto, C., 1983, Accumulation of guanosine-cytosine enriched low MW DNA fragments in lymphocytes of patients with SLE, J. Immunol. 130: 187–190.PubMedGoogle Scholar
  58. Schecter, Y., Maron, R., Elias, D., and Cohen, I. R., 1982, Autoantibodies to insulin receptor spontaneously develop as anti-idiotypes in mice immunized with insulin, Science 216: 452–454.Google Scholar
  59. Schoenfeld, Y., Rauch, J., Massicotte, H., Datta, S. K., Andre-Schwartz, J., Stollar, B. D., and Schwartz, R. S., 1983, Poly specificity of monoclonal lupus antibodies produced by human-human hybridomas, N. Engl. J. Med. 308: 414–418.CrossRefGoogle Scholar
  60. Seligmann, M., 1957, Mise en evidence dans le serum de malades atteints de lupus erythemateux dissemine d’une substance determinant une reaction de precipitation avec l’acide desoxyribonucleique, C. R. Acad. Sci. (D) (Paris) 245: 243–247.Google Scholar
  61. Slack, J. H., Hang, L., Barkley, J., Fulton, R. J., D’Hoostelaere, L., Robinson, A., and Dixon, F. J., 1984, Isotypes of spontaneous and mitogen-induced autoantibodies in SLE-prone mice, J. Immunol. 132: 1271–275.PubMedGoogle Scholar
  62. Solomon, G., Schiffenbauer, J., Keiser, H. D., and Diamond, B., 1983, Use of monoclonal antibodies to identify shared idiotypes on human antibodies to DNA from patients with SLE, Proc. Natl. Acad. Sci. U.S.A. 80: 850–853.PubMedCrossRefGoogle Scholar
  63. Sonteheimer, R. D., and Gilliam, J. N., 1978, DNA antibody class, subclass, and complement fixation in SLE with and without nephritis, Clin. Immunol. Immunopathol. 10: 459–467.CrossRefGoogle Scholar
  64. Steinberg, A. D., Raveche, E. S., Laskin, C. A., Miller, M. L., and Steinberg, R. T., 1982, Genetic, environmental, and cellular factors in the pathogenesis of SLE, Arthritis Rheum. 25: 734–743.PubMedCrossRefGoogle Scholar
  65. Stollar, B. D., 1980, Reaction of systemic lupus erythematosus antinative DNA antibodies with native DNA fragments from 20 to 1200 base pairs, J. Clin. Invest. 65: 469–477.PubMedCrossRefGoogle Scholar
  66. Talal, N., 1980, Tolerance and autoimmunity, in: Clinical Immunology ( C. P. Parker, ed.), W. B. Saunders, Philadelphia, pp. 105–109.Google Scholar
  67. Talal, N., Dauphinee, M. J., and Wofsy, D., 1982, Interleukin-2 deficiency, genes, and SLE, Arthritis Rheum. 25: 838–842.PubMedCrossRefGoogle Scholar
  68. Tan, E. M., 1976, Sunlight as a potential aetiological factor in systemic lupus erythematosus, in: Modern Topics in Rheumatology ( G. R. Hughes, ed.), Year Book Publishers, Chicago, pp. 99–106.Google Scholar
  69. Tan, E. M., Schur, P. H., Carr, R. H., and Kunkel, H. G. 1966, DNA and antibodies to DNA in the serum of patients with SLE, J. Clin. Invest. 45: 1732–1740.PubMedCrossRefGoogle Scholar
  70. Taylor, R. P., Weber, D., Broccoli, A. V., and Winfield, J. R., 1979, Stability of DNA/anti-DNA complexes, J. Immunol. 122: 115–120.PubMedGoogle Scholar
  71. Teitelbaum, D., Rauch, J., Stollar, B. D., and Schwartz, R. J. 1984, In vivo effects of antibodies against a high frequency idiotype of anti-DNA antibodies in MRL mice, J. Immunol. 132: 1282–1285.PubMedGoogle Scholar
  72. Theofilopoulus, A. N., Shawler, D. L., Eisenberg, R. A., and Dixon, F. J., 1980, Splenic immunoglobulin secreting cells and their regulation in autoimmune mice, J. Exp. Med. 151: 446–466.CrossRefGoogle Scholar
  73. Weisbart, R. H., Garrett, R. A., Leibling, M. R., Barnett, E. V., Paulus, H. E., and Katz, D. H., 1983, Specificity of anti-nucleoside antibodies in SLE, Clin. Immunol. Immunopathol. 27: 403–411.PubMedCrossRefGoogle Scholar
  74. Williams, R. C., Jr., 1982, Cellular mechanism of tissue injury and immune derangement in SLE, Arthritis Rheum. 25: 810–813.PubMedCrossRefGoogle Scholar
  75. Wilson, J. G., Wong, W. W., Schur, P. H., and Fearon, D. T., 1982, Mode of inheritance of decreased C3b Receptors on erythrocytes of patients with systemic lupus erythematosus, N. Engl. J. Med. 307: 981–985.PubMedCrossRefGoogle Scholar
  76. Winfield, J. B., Faiferman, J., and Koffler, D., 1977, Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with SLE. Association of high avidity anti-native DNA antibody with glomerulonephritis, J. Clin. Invest. 59: 90–96.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1985

Authors and Affiliations

  • Bevra H. Hahn
    • 1
  1. 1.Department of Medicine, Division of RheumatologyUniversity of CaliforniaLos AngelesUSA

Personalised recommendations