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False-negative anti-DNA antibody activity in infantile systemic Lupus erythematosus (SLE)

Abstract

A 2.5-month-old previously healthy female infant presented with serositis, nephrotic syndrome, progressive renal failure, anemia, and thrombocytopenia. Renal biopsy revealed a proliferative glomerulonephritis with glomerular and extraglomerular deposits of IgG, IgM, C3, and Clq by direct immunofluorescence (IF) techniques. Skin biopsy was positive for IgG and C3 deposits in the dermal-epidermal junction by IF. Despite strong clinical and pathological criteria for systemic lupus erythematosus (SLE), tests for antinuclear and anti-DNA antibodies were negative. Circulating immune complexes (CICs) were detected in three separate assay systems. Immunochemical analysis of isolated CICs showed that anti-DNA antibody was present. Analysis of kidney biopsy material by antigen-specific solubilization techniques showed antibodies reactive with ds-DNA in the kidney. These studies confirm that SLE may be a cause of the congenital nephrotic syndrome and that negative SLE serologies may be secondary to binding of available antibody by excess antigen. Analysis of CICs may be helpful in confirming the diagnosis of SLE in seronegative patients.

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References

  1. 1.

    Arnett FC, Shulman LE: Studies in familial systemic lupus erythematosus. Medicine 55:313–321, 1976

  2. 2.

    Schaller JG: Lupus phenomena in the newborn. Proceedings of the First Conference of Childhood Rheumatic Diseases. Arth Rheum (Suppl) 20:312–318, 1977

  3. 3.

    Schaller JG: Lupus in childhood. Clin Rheum Dis 8:219–228, 1982

  4. 4.

    Altenburger KM, Jedzinia KM, Roper WL, Hernandez J: Congenital complete heart block associated with hydrops fetalis. J Pediat 91:618–620, 1977

  5. 5.

    Hogg GR: Congenital acute lupus erythematosus associated with subendocardial fibroelastosis. Report of a case. Am J Clin Pathol 28:648–654, 1957

  6. 6.

    Grossman J, Schwartz R, Callerame M, Condemi JJ: Systemic lupus erythematosus in a 1 year old child. Am J Dis Child 129:123–125, 1975

  7. 7.

    Ty A, Fine B: Membranous nephritis in infantile systemic lupus erythematosus associated with chromosomal abnormalities. Clin Nephrol 12:137–141, 1979

  8. 8.

    Barnett EV, Condemi JJ, Leddy JP,et al.: Gamma2, gamma1a and gamma1m antinuclear factors in human sera. J Clin Invest 43:1104–1115, 1964

  9. 9.

    Seligmann M, Cannat A, Hammond M: Studies on antinuclear antibodies. Ann NY Acad Sci 124:816–832, 1965

  10. 10.

    Friou JG: Antinuclear antibodies: Diagnostic significance and methods. Arth Rheum 10:151–156, 1967

  11. 11.

    Leonhardt T: Family studies in systemic lupus erythematosus. Acta Med Scand (Suppl) 416:95, 1964

  12. 12.

    Pollak VE: Antinuclear antibodies in families of patients with systemic lupus erythematosus. N Engl J Med 271:165–171, 1964

  13. 13.

    Maddison PJ: ANA-negative SLE. Clin Rheum Dis 8:105–115, 1982

  14. 14.

    Gilespie JP, Lindsley CB, Linshaw MA, Richardson WP: Childhood systemic lupus erythematosus with negative antinuclear antibody test. J Pediat 98:578–581, 1981

  15. 15.

    Blomjous FJEM, Feltkamp-Vroom TM: Hidden antinuclear antibodies in seronegative systemic lupus erythematosus patients and in NZB, and (NZB × NZW)F1 mice. Eur J Immunol 1:396–398, 1971

  16. 16.

    Svec KH, Blair JD, Kaplan MH: Immunopathologic studies of systemic lupus erythematosus (SLE). I. Tissue-bound immunoglobulins in relation to serum antinuclear immunoglobulins in systemic lupus and chronic liver disease with LE cell factor. J Clin Invest 46:558–568, 1967

  17. 17.

    Tron F, Letarte J, Roque-Antunes Barrina MC, Lesavre, Inserm P: Specific detection of DNA: Anti-DNA immune complexes in human systemic lupus erythematosus sera using murine monoclonal anti-DNA antibody. Clin Exp Immunol 49:481–487, 1982

  18. 18.

    Tan EM, Schur PH, Carr RI, Kunkel HG: Deoxyribonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J Clin Invest 45:1732–1740, 1966

  19. 19.

    Krishnan CS, Kaplan MH: Immunopathologic studies of systemic lupus erythematosus. II. antinuclear reaction of gamma-globulin eluted from homogenates and isolated glomeruli of kidneys from patients with lupus nephritis. J Clin Invest 46:569–579, 1967

  20. 20.

    Landry M, Sams WM Jr: Systemic lupus erythematosus. Studies of antibodies bound to skin. J Clin Invest 52:1871–1880, 1973

  21. 21.

    Harbeck RJ, Bardana EJ, Kohler PF, Carr RI: DNA-anti-DNA complexes: Their detection in systemic lupus erythematosus. J Clin Invest 52:789–795, 1973

  22. 22.

    Izui S, Lambert PH, Miescher PA: Failure to detect circulating DNA-anti-DNA complexes in systemic lupus erythematosus. Clin Exp Immunol 30:384–392, 1977

  23. 23.

    Davis JS, Godfrey SM, Winfield JB: Direct evidence for circulating DNA/anti-DNA complexes in systemic lupus erythematosus. Arth Rheum 21:17–22, 1978

  24. 24.

    Jordan SC, Buckingham B, Sakai RS, Olson D: Studies of glomerulonephritis mediated by human thyroglobulin. N Engl J Med 304:1212–1215, 1981

  25. 25.

    Penner E, Boris A, Glurich I, Andres GA, Milgrom F: Dissociation of Immune complexes in tissue sections by excess antigen. Int Arch Allergy Appl Immunol 67:245–253, 1982

  26. 26.

    Jordan SC, Sakai RS, Ettenger RB, Fine RN: Characterization of soluble circulating immune complexes by antigen-specific dissociation: Detection in the Raji cell radioimmune assay. Clin Immunol Immunopathol 27:357–358, 1983

  27. 27.

    Deline M, Cambiaso CL, Masson PL: Circulating immune complexes in infants fed on cows milk. Nature Lond 272:632–634, 1978

  28. 28.

    Theofilopoulos AN, Wilson CB, Dixon FJ: The Raji cell radioimmune assay for detecting immune complexes in human sera. J Clin Invest 37:169–182, 1976

  29. 29.

    Hay FC, Nineham LS, Roitt IM: Routine assay for the detection of immune complexes of known immunoglobulin class using solid phase Clq. Clin Exp Immunol 27:396–400, 1976

  30. 30.

    Jordan SC, Sakai R, Ettenger RB,et al.: Circulating immune complexes in pediatric renal allograft recipients. Transplantation 31:190–194, 1981

  31. 31.

    Theofilopoulos AN, Pereira B, Eisenberg RA, Dixon FJ: Immune complex assays.In Manual of Clinical Immunology, N Rose, H Friedman (eds). Washington, DC, 1980, pp 186–192

  32. 32.

    Pincus T, Schur PH, Rose JA,et al.: Measurement of serum DNA binding activity in systemic lupus erythematosus. N Engl J Med 281:701–705, 1969

  33. 33.

    Bergstein J, Litman N: Interstitial nephritis with anti-tubular basement membrane antibody. N Engl J Med 292:875–878, 1975

  34. 34.

    Milgrom F, Campbell WA, Andres GA: Antigen in immune complex glomerulonephritis. V. Recovery and identification by gel precipitation. Immunology 30:277–280, 1976

  35. 35.

    Roberts J, Edmund J: Immunochemical demonstration of cryoprecipitable anti-native DNA antibody and DNA in the serum of patients with glomerulonephritis. J Immunol 124:127–130, 1980

  36. 36.

    Phillips T, Draper C: Circulating immune complexes in schistosomiasis due toSchistosoma Mansoni. Br Med J 2:476–477, 1975

  37. 37.

    Woodroffe AJ, Wilson CB: An evaluation of elution techniques in the study of immune complex glomerulonephritis. J Immunol 118:1788–1794, 1977

  38. 38.

    Inman R: Immune complexes in SLE. Clin Rheum Dis 8:49–62, 1982

  39. 39.

    Koffler D, Angello V, Thoburn R, Kunkel HG: Systemic lupus erythematosus: Prototype of immune complex nephritis in man. J Exp Med 134:169s-179s, 1971

  40. 40.

    Sano H, Morimoto C: Isolation of DNA from DNA/anti-DNA antibody immune complexes in systemic lupus erythematosus. J Immunol 126:538–539, 1981

  41. 41.

    Abdou NI, Wall H, Lindsley HH, Halsey JF, 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 67:1297–1304, 1981

  42. 42.

    Izui S, Eisenberg R: Circulating anti-DNA-rheumatoid factor complexes in MRL-1 mice. Clin Immunol Immunopathol 15:536–551, 1980

  43. 43.

    Tan EM, Cohen AS, Fries JF,et al.: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arth Rheum 25:1271–1277, 1982

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Correspondence to S. C. Jordan.

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Jordan, S.C., Lemire, J.M., Border, W. et al. False-negative anti-DNA antibody activity in infantile systemic Lupus erythematosus (SLE). J Clin Immunol 4, 156–162 (1984). https://doi.org/10.1007/BF00915050

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Key words

  • Infantile systemic lupus erythematosus (SLE)
  • congenital nephrotic syndrome
  • circulating immune complexes
  • false-negative anti-DNA