Advertisement

New Concepts in the Etiopathogenesis of Systemic Lupus Erythematosus

  • Jean-Paul Viard
  • Laurent Jacob
  • Jean-François Bach

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized clinically by multiple organ involvement and biologically by the production of a wide spectrum of autoantibodies directed against different cell types and cellular antigens, notably nuclear antigens. Polyclonal B cell hyperactivation is considered as the immunological cornerstone of the disease, both in humans and animal models (1).

Keywords

Systemic Lupus Erythematosus Systemic Lupus Erythematosus Patient Lupus Nephritis Cyproterone Acetate Total Lymphoid Irradiation 
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. 1.
    Bach JF. Pathology of Immune Complexes. Systemic Lupus Erythematosus. In: Bach JF, ed. New York: Wiley Medical Publishers, 1982.Google Scholar
  2. 2.
    Theofilopoulos AN, Dixon FJ. Murine models of systemic lupus erythematosus. Adv Immunol 1985; 37: 269–390.CrossRefGoogle Scholar
  3. 3.
    Gavalchin J, Seder RA, Datta SK. The NZB x SWR model of lupus nephritis. I. Cross-reactive idiotypes of monoclonal anti-DNA antibodies in relation to antigenic specificity, charge, and allotype. Identification of interconnected idiotype families inherited from the normal SWR and the autoimmune NZB parents. J Immunol 1987; 128: 128–137.Google Scholar
  4. 4.
    Gavalchin J, Datta SK. The NZB x SWR model of lupus nephritis. II. Autoantibodies deposited in renal lesions show a distinctive and restricted idiotypic diversity. J Immunol 1987; 128: 138–48.Google Scholar
  5. 5.
    Sidman CL, Shultz LD, Hardy RR, Hayakawa K, Herzenberg LA. Production of immunoglobulin isotypes by Ly-1 + B cells in viable Motheaten and normal mice. Science 1986; 232: 1423–5.CrossRefGoogle Scholar
  6. 6.
    Tron F, Bach FJ. Relationships between antibodies to native DNA and glomerulonephritis in systemic lupus erythematosus. Clin Exp Immunol 1977; 28: 426–32.Google Scholar
  7. 7.
    Tron F, Jungers P, Droz D, Bach JF. Valeur des tests immunologiques dans la surveillance du traitement du lupus érythémateux disséminé. Nouv Presse Méd 1980; 9: 2319–23.Google Scholar
  8. 8.
    Lightfoot RW, Hughes GRV. Significance of persisting serologic abnormalities in systemic lupus erythematosus. Arthritis Rheum 1976; 19: 837–43.CrossRefGoogle Scholar
  9. 9.
    Lambert PH, Dixon FJ. Pathogenesis of glomerulonephritis of NZB/W mice. J Exp Med 1968; 127: 507–22.CrossRefGoogle Scholar
  10. 10.
    Koffler D, Agnello V, Kunkel HG. Polynucleotide immune complexes in serum and glomeruli of patients with systemic lupus erythematosus. Am J Pathol 1974; 74: 109–24.Google Scholar
  11. 11.
    Krishnan CS, Kaplan MH. Immunopathologic studies of systemic lupus erythematosus. II. Antinuclear reaction of globulin eluted from homogenates and isolated glomeruli of kidneys from patients with lupus nephritis. J Clin Invest 1967; 46: 569–79.CrossRefGoogle Scholar
  12. 12.
    Bruneau C, Benveniste J. Circulating DNA-anti-DNA complexes in systemic lupus erythematosus. Detection and characterization by ultracentrifugation. J Clin Invest 1979; 64: 191–8.CrossRefGoogle Scholar
  13. 13.
    Tron F, Letarte J, Roque-Antunes MC, Lesavre P. Specific detection of DNA-anti-DNA immune complexes in human SLE sera using murine monoclonal antibody. Clin Exp Immunol 1982; 49: 481–7.Google Scholar
  14. 14.
    Izui S, Lambert PH, Miescher PA. Failure to detect circulating DNA-anti-DNA complexes in systemic lupus erythematosus. Clin Exp Immunol 1977; 30: 388–92.Google Scholar
  15. 15.
    Izui S, Lambert PH, Miescher PA. In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA: a possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus. J Exp Med 1977; 144: 428–43.CrossRefGoogle Scholar
  16. 16.
    Izui S, Lambert PH, Türler H, Miescher PA. Features of systemic lupus erythematosus in mice injected with bacterial lipopolysaccharides. Identification of circulating DNA and renal localization of DNA-anti-DNA complexes. J Exp Med 1977; 145: 1115–30.CrossRefGoogle Scholar
  17. 17.
    Hahn BH. Characteristics of pathogenic subpopulations of antibodies to DNA. Arthritis Rheum 1982; 25: 747–52.CrossRefGoogle Scholar
  18. 18.
    Gavalchin J, Nicklas JA, Eastcott JW, et al. Lupus prone (SWR x NZB)F1 mice produce potentially nephritogenic autoantibodies inherited from the normal SWR parent. J Immunol 1985; 134: 885–94.Google Scholar
  19. 19.
    Livneh A, Halpern A, Lazo A, Halpern R, Diamond B. Monoclonal antibody to a cross-reactive idiotype on cationic human anti-DNA antibodies expressing lambda light chains: a new reagent to identify a potentially differential pathogenic subset. J Immunol 1987; 138: 123–7.Google Scholar
  20. 20.
    Hahn BH, Ebling FM. Suppression of murine lupus nephritis by administration of an anti-idiotypic antibody to anti-DNA. J Immunol 1984; 132: 187–90.Google Scholar
  21. 21.
    Bach JF, Jacob L, Feutren G, Tron F. The questionable role of anti-DNA antibodies in the pathogenesis of systemic lupus erythematosus. In: Schwartz RS, Rose NR, eds. Autoimmunity: Experimental and Clinical Aspects. Ann NY Acad Sci 1986; 475: 231–40.Google Scholar
  22. 22.
    Brennan FM, Williams DG, Bovill D, Stocks MR, Maini RN. Administration of monoclonal anti-Sm antibody prolongs the survival and renal function of MRL-lpr/lpr mice. Clin Exp Immunol 1986; 65: 42–50.Google Scholar
  23. 23.
    Stocks MR, Williams DG, Maini RN. Differential induction of lupus associated antinuclear autoantibodies in MRL mice by monoclonal anti-Sm antibodies. Clin Exp Immunol 1987; 67: 492–9.Google Scholar
  24. 24.
    Stollar BD. Nucleic Acid Antigens. In: Sela M, ed. The antigens. London: Academic Press, 1973; Vol. 1: 1–84.Google Scholar
  25. 25.
    Lafer EM, Rauch J, Andrzejewski C, et al. Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids. J Exp Med 1981; 153: 897–909.CrossRefGoogle Scholar
  26. 26.
    Faaber P, Capel PJA, Rijke GPM, Vierwinden G, Van de Putte LBA, Koene RAP. Crossreactivity of anti-DNA antibodies with proteoglycans. Clin Exp Immunol 1984; 55: 502–8.Google Scholar
  27. 27.
    Naparstek Y, Duggan D, Schattner A, et al. Immunochemical similarities between monoclonal antibacterial Waldenström’s macroglobulins and monoclonal anti-DNA lupus autoantibodies. J Exp. Med 1985; 161: 1525–38.CrossRefGoogle Scholar
  28. 28.
    Schoenfeld Y, Vilner Y, Coates ARM, et al. Monoclonal antituberculosis antibodies react with DNA, and monoclonal anti-DNA autoantibodies react with Mycobacterium tuberculosis. Clin Exp Immunol 1986; 66: 255–61.Google Scholar
  29. 29.
    Darwin BS, Grudier JP, Klatt CL, Pisetsky DS. IgG antinuclear antibodies with cross-reactive rheumatoid factor activity. J Immunol 1986; 137: 3796–801.Google Scholar
  30. 30.
    Jacob L, Tron F, Bach JF, Louvard D. A monoclonal anti-DNA antibody also binds to cell-surface protein(s). Proc Natl Acad Sci USA 1984; 81: 3843–5.CrossRefGoogle Scholar
  31. 31.
    Dixon, FL. Murine lupus. A model for human autoimmunity. Arthritis Rheum 1985; 28: 1081–8.CrossRefGoogle Scholar
  32. 32.
    Shirai T, Ohta K, Kohno A, et al. Naturally occurring antibody response to DNA is associated with the response to retroviral gp70 in autoimmune New Zealand mice. Arthritis Rheum 1986; 29: 242–50.CrossRefGoogle Scholar
  33. 33.
    Jungers P, Nahoul K, Pelissier C, Dougados M, Tron F, Bach JF. Low plasma androgens in women with active or quiescent systemic lupus erythematosus. Arthritis Rheum 1982; 25: 454–7.CrossRefGoogle Scholar
  34. 34.
    Melez KA, Deleargyros N, Bellanti JA, Goldstein AL, Smathers P, Steinberg AD. Effect of partial testosterone replacement or thymosin on anti-DNA in castrated (NZB x NZW)F1 males. Clin Immunol Immunopathol 1987; 42: 319–27.CrossRefGoogle Scholar
  35. 35.
    Datta SK, Patel H, Berry D. Induction of a cationic shift in IgG anti-DNA autoantibodies. Role of T helper cells with classical and novel phenotype in three models of lupus nephritis. J Exp Med 1987; 165: 1252–68.CrossRefGoogle Scholar
  36. 36.
    Jacob L, Tron F. Monoclonal anti-deoxyribonucleic antibodies. I. Isotope and specificity studies. J Immunol 1982; 128: 895–8.Google Scholar
  37. 37.
    Jacob L, Léty MA, Louvard D, Bach JF. Binding of a monoclonal anti-DNA autoantibody to identical protein(s) present at the surface of several human cell types involved in lupus pathogenesis. J Clin Invest 1985; 75: 315–7.CrossRefGoogle Scholar
  38. 38.
    Jacob L, Léty MA, Bach JF, Louvard D. Human systemic lupus erythematosus sera contain antibodies against cell-surface protein(s) that shar(s) epitope(s) with DNA. Proc Natl Acad Sci USA 1986; 83: 6970–4.CrossRefGoogle Scholar
  39. 39.
    Jacob L, Léty MA, Monteiro RC, Jacob F, Bach JF, Louvard D. Altered cell-surface protein(s), crossreactive with DNA, on spleen cells of autoimmune lupic mice. Proc Natl Acad Sci USA 1987; 84: 1361–3.CrossRefGoogle Scholar
  40. 40.
    Jacob L, Léty MA, Choquette D, et al. Presence of antibodies against a cell-surface protein, cross-reactive with DNA, in systemic lupus erythematosus: a marker of the disease. Proc Natl Acad Sci USA 1987; 84: 2956–9.CrossRefGoogle Scholar
  41. 41.
    Viard JP, Bach JF, Jacob L. Splenocytes from MRL/Mp/lpr/lpr mice spontaneously produce antibodies against a cell-surface protein cross-reacting with DNA. Clin Immunol Immunopathol; in press.Google Scholar
  42. 42.
    Austin HA, Klippel JH, Balow JE, et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986; 314: 614–9.CrossRefGoogle Scholar
  43. 43.
    Kotzin BL, Arndt R, Okada S, Ward R, Thach AB, Strober S. Treatment of NZB/NZW mice with total lymphoid irradiation: long-lasting suppression of disease without generalized immune suppression. J Immunol 1986; 136: 3259–65.Google Scholar
  44. 44.
    Ben-Chetrit E, Gross DJ, Braverman A, et al. Total lymphoid irradiation in refractory systemic lupus erythematosus. Ann Intern Med 1986; 105: 58–60.Google Scholar
  45. 45.
    Jungers P, Kutenn F, Liote F, et al. Hormonal modulation in systemic lupus erythematosus. Preliminary clinical and hormonal results with cyptroterone acetate. Arthritis Rheum 1985; 28: 1243–50.CrossRefGoogle Scholar
  46. 46.
    Israel-Biet D, Noël LH, Bach MA, Dardenne M, Bach JF. Marked reduction of DNA antibody production and glomerulopathy in thymulin (FTS-Zn) or cyclosporin A treated (NZB x NZW)F1 mice. Clin Exp Immunol 1983; 54: 359–65.Google Scholar
  47. 47.
    Mountz JD, Smith HR, Wilder RL, Reeves JP, Steinberg AD. Cs-A therapy in MRL-lpr/lpr mice: amelioration of immunopathology despite autoantibody production. J Immunol 1987; 138: 157–63.Google Scholar
  48. 48.
    Wofsy D, Seaman WE. Reversal of advanced murine lupus in NZB/NZW F1 mice by treatment with monoclonal antibody to L3T4. J Immunol 1987; 138: 3247–53.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Jean-Paul Viard
    • 1
  • Laurent Jacob
    • 1
  • Jean-François Bach
    • 1
  1. 1.Hôpital NeckerINSERM U 25Paris Cedex 15France

Personalised recommendations