Anti-glomerular Basement Disease: Goodpasture’s Syndrome

  • Gangadhar Taduri
  • Raghu Kalluri
  • Ralph J. Panos
Part of the Respiratory Medicine book series (RM)


Goodpasture’s syndrome is an exemplary rare lung and kidney disease that has led to significant discoveries in human biology. The initial observations that antibodies directed against glomerular basement membrane (GBM) caused glomerulonephritis stimulated evaluation of the components of the basement membrane, elucidation of the reticular collagen network, and identification of different types of collagen. The α3[IV] NC1 domain of type IV collagen is the antigenic epitope that initiates a complex autoimmune reaction culminating in the clinical manifestations of Goodpasture’s syndrome. Immunization with α3[IV] collagen has provided an experimental model that has led to fundamental discoveries into the genetic and immune processes precipitating and modulating autoimmune diseases. Initial evaluation of the autoimmune process focused on humoral mechanisms, but more recent studies suggest that the cellular immune process is activated and plays a key role in the pathogenesis of Goodpasture’s syndrome. Hemoptysis occurs in nearly all patients and renal histopathology demonstrates crescentic glomerulonephritis in the majority of cases. Immunofluorescence microscopy reveals the pathognomonic finding of linear deposition of IgG along with the glomerular capillaries and in the lung parenchyma. The diagnosis of anti-GBM disease is confirmed by the presence of circulating antibodies against basement membrane antigen in the correct clinical setting. Based on the pathogenetic mechanisms, therapeutic modalities include both induction and maintenance regimens: induction or initial therapy removes the pathogenic anti-GBM antibody by plasmapheresis and maintenance therapy reduces antibody production by immunosuppression. The prognosis of patients with anti-GBM disease depends on the level of renal dysfunction at presentation.


Goodpasture’s syndrome anti-glomerular basement membrane disease type IV collagen pulmonary–renal syndrome autoimmune disorder 


  1. 1.
    Brainwood D, Kashtan C, Gubler MC, et al. Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation. Kidney Int 1998;53:762–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Peten E, Pirson Y, Cosyns JP, et al. Outcome of thirty patients with Alport’s syndrome after renal transplantation. Transplantation 1991;52:823–6.CrossRefPubMedGoogle Scholar
  3. 3.
    3.Goodpasture EW. The pathology of pneumonia accompanying influenza. US Naval Med Bull 1919;13:177–97.Google Scholar
  4. 4.
    Stanton MC, Tange JD. Goodpasture’s syndrome: pulmonary hemorrhage associated with glomerulonephritis. Austr Ann Med 1958;7:132–44.Google Scholar
  5. 5.
    5.Hudson BG, Reeders ST, et al. Type IV collagen: Structure, gene organization, and role in human diseases. Molecular basis of Goodpasture and Alport syndromes and diffuse leiomyomatosis. J Biol Chem 1993 Dec 15;268(35):26033–6.PubMedGoogle Scholar
  6. 6.
    Groffen AJ, Veerkamp JH, et al. Recent insights into the structure and functions of heparan sulfate proteoglycans in the human glomerular basement membrane. Nephrol Dial Transplant 1999 Sep;14(9):2119–29.CrossRefPubMedGoogle Scholar
  7. 7.
    Hudson BG. The molecular basis of Goodpasture and Alport syndromes: Beacons for the discovery of the collagen IV family. J Am Soc Nephrol 2004 Oct;15(10):2514–27.CrossRefPubMedGoogle Scholar
  8. 8.
    Rutgers A, Meyers KE, Cabziani G, Aklluri R, Lin J, Madaio MP. High affinity of anti-GBM antibodies from Goodpasture and transplanted Alport patients to alpha3[IV]NC1 collagen. Kidney Int 2000;58:115.CrossRefPubMedGoogle Scholar
  9. 9.
    Neilson EG, Kalluri R, Sun MJ, Gunwar S, Danoff T, Mariayama M, Myers JC, Reeders ST, Hudson BG. Specificity of Goodpasture autoantibodies for the recombinant noncollagenous domains of human type IV collagen. J Biol Chem 1993;268:8402.PubMedGoogle Scholar
  10. 10.
    Turner N, Forstova J, Rees A, Pusy CD Mason PJ. Production and characterization of recombinant Goodpasture antigen in insect cells. J Biol Chem 1994;269:17141.PubMedGoogle Scholar
  11. 11.
    Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen. N Engl J Med 2003;348:2543.CrossRefPubMedGoogle Scholar
  12. 12.
    Kalluri R, Wilson CB, Weber M,Gunwar S, Chonko AM, Neilson EG, Hudson BG. Identification of the alpha 3 chain of type IV collagen as the common autoantigen in antibasement membrane disease and Goodpasture syndrome. J Am Soc Nephrol 1995;6:1178.PubMedGoogle Scholar
  13. 13.
    Bolton WK. Goodpasture’s syndrome. Kidney Int 1996;50:1753.CrossRefPubMedGoogle Scholar
  14. 14.
    Pusey CD. Anti-glomerular basement membrane disease. Kidney Int 2003;64:1535.CrossRefPubMedGoogle Scholar
  15. 15.
    Umekawa T, Kohri K, Yoshioka K, Iguchi M, Kurita T. Production of anti-glomerular basement membrane antibody after extracorporeal shock wave lithotripsy. Urol Int 1994;52:106.CrossRefPubMedGoogle Scholar
  16. 16.
    Kjaluuri R, Cantley LG, Kerjaschki D, Neilson EG. Reactive oxygen species expose cryptic epitopes associated with autoimmune Goodpasture syndrome. J Biol Chem 2000 Jun 30;275(26):20027–32.CrossRefGoogle Scholar
  17. 17.
    Hopfer H, Maron R, Butzmann U, Helmchen U, Weiner HL, Kalluri R. The importance of cell-mediated immunity in the course and severity of autoimmune anti-glomerular basement membrane disease in mice. FASEB J 2003 May;17(8):860–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Hosken NA, Shibuya K, Heath AW, Murphy KM, O’Garra A. The effect of antigen dose on CD4_T helper cell phenotype development in a T cell receptor-alpha beta-transgenic model. J Exp Med 1995;182:1579–84.CrossRefPubMedGoogle Scholar
  19. 19.
    Schweitzer AN, Borriello F, Wong RC, Abbas AK, Sharpe AH. Role of costimulators in T cell differentiation: Studies using antigen-presenting cells lacking expression of CD80 or CD86. J Immunol 1997;158:2713–22.PubMedGoogle Scholar
  20. 20.
    McDevitt HO. The role of MHC class II molecules in susceptibility and resistance to autoimmunity. Curr Opin Immunol 1998;10:677–81.CrossRefPubMedGoogle Scholar
  21. 21.
    Batista FD, Neuberger MS. Affinity dependence of the B cell response to antigen: A threshold, a ceiling, and the importance of off-rate. Immunity 1998;8:751–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Science 1996;383:787–93.Google Scholar
  23. 23.
    Holdsworth SR, Kitching AR, Tipping PG. Th1 and Th2 T helper cell subsets affect patterns of injury and outcomes in glomerulonephritis. Kidney Int 1999;55:1198–216.CrossRefPubMedGoogle Scholar
  24. 24.
    Kalluri R, Danoff TM, Okada H, Neilson EG. Susceptibility to anti-glomerular basement membrane disease and Goodpasture syndrome is linked to MHC class II genes and the emergence of T cell-mediated immunity in mice. J Clin Invest 1997 Nov 1;100(9):2263–75.CrossRefPubMedGoogle Scholar
  25. 25.
    Weber M, Lohse AW, Manns M, Meyer zum Buschenfelde KH, Kohler H. IgG subclass distribution of autoantibodies to glomerular basement membrane in Goodpasture’s syndrome compared to other autoantibodies. Nephron 1988;49:54–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Huang XR, Tipping PG, Shuo L, Holdsworth SR. Th1 responsiveness to nephritogenic antigens determines susceptibility to crescentic glomerulonephritis in mice. Kidney Int 1997 Jan;51(1):94–103.CrossRefPubMedGoogle Scholar
  27. 27.
    Ruth AJ, Kitching AR, Semple TJ, Tipping PG, Holdsworth SR. Intrinsic renal cell expression of CD40 directs Th1 effectors inducing experimental crescentic glomerulonephritis. J Am Soc Nephrol 2003 Nov;14(11):2813–22.CrossRefPubMedGoogle Scholar
  28. 28.
    Kitchig AR, Turner AL, Semple T, Li M, Edftton KL, Wilson GR, Timoshanko JR, Hudson BG, Holdsworth SR. Experimental autoimmune anti-glomerular basement membrane glomerulonephritis: A protective role for IFN-gamma. J Am Soc Nephrol 2004 Jul;15(7):1764–4.CrossRefGoogle Scholar
  29. 29.
    Kitching AR, Tipping PG, Timoshanko JR, Holdsworth SR. Endogenous interleukin-10 regulates Th1 responses that induce crescentic glomerulonephritis. Kidney Int 2000 Feb;57(2):518–25.CrossRefPubMedGoogle Scholar
  30. 30.
    Salama AD, Chaudhry AN, Holthaus KA, Mosley K, Kalluri R, Sayegh MH, Lechler RL, Pusey CD, Lightstone L. Regulation by CD25+ lymphocytes of autoantigen-specific T-cell responses in Goodpasture’s [anti-GBM] disease. Kidney Int 2003 Nov;64(5):1685–94.CrossRefPubMedGoogle Scholar
  31. 31.
    Phelps RG, Rees AJ. The HLA complex in Goodpasture’s disease: A model for analyzing susceptibility to autoimmunity. Kidney Int 1638;1999:56.Google Scholar
  32. 32.
    Fisher M, Pusey CD, Vaughan RW, Rees AJ. Susceptibility to anti-glomerular basement membrane disease is strongly associated with HLA-DRB1 genes. Kidney Int 1997;51:222.CrossRefPubMedGoogle Scholar
  33. 33.
    Kalluri R, Danoff TM, Okada H, Neilson EG. Susceptibility to cell-mediated inflammation in murine anti-glomerular basement membrane disease is linked to MHC Aa/Ab and the emergence of an IGg2a/Th1 effect. J Clin Invest 1997;100:2263.CrossRefPubMedGoogle Scholar
  34. 34.
    Reynolds J, Albouainain A, Duda MA, Evans DJ, Pusy CD. Strain susceptibility to active induction and passive transfer of experimental autoimmune glomerulonephritis in the rat. Nephrol Dial Transplant 2006 Dec;21(12):3398–408.CrossRefPubMedGoogle Scholar
  35. 35.
    Mcleish KR, Yum MN, Luft FC. Rapidly progressive glomerulonephritis in adults: Clinical and histologic correlations. Clin Nephrol 1978;10:43.PubMedGoogle Scholar
  36. 36.
    Niles JL, Bottinger EP, Saurina GR, Kelly KJ, Pan G, Collins AB, Mc Cluskey RT. The syndrome of lung hemorrhage and nephritis is usually an ANCA-associated condition. Arch Intern Med 1996;156:440.CrossRefPubMedGoogle Scholar
  37. 37.
    Levy JB, Turner AN, Rees AJ, Pusey CD. Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression. Ann Intern Med 2001;134:1033.PubMedGoogle Scholar
  38. 38.
    Savage CO, Pusey CD, Bowman C, et al. Antiglomerular basement membrane antibody-mediated disease in the British Isles 1980–1984. Br Med J [Clin Res Ed] 1986;292(6516):301–4.CrossRefGoogle Scholar
  39. 39.
    Salant DJ. Immunopathogenesis of crescentic glomerulonephritis and lung purpura. Kidney Int 1987;32:408.CrossRefPubMedGoogle Scholar
  40. 40.
    Kalluri R, Weber M, Netzer KO, Sun MJ, Neilson EG, Hudson BG. COL4A5 gene deletion and production of post-transplant anti-alpha 3[IV] collagen alloantibodies in Alport syndrome. Kidney Int 1994;45:721.CrossRefPubMedGoogle Scholar
  41. 41.
    Benoit FL, Rulon DB, Theil GB, et al. Goodpasture’s syndrome: A clinicopathologic entity. Am J Med 1963;58:424–44.Google Scholar
  42. 42.
    Proskey AJ, Weatherbee L, Easterling RE, et al. Goodpasture’s syndrome: A report of five cases and review of the literature. Am J Med 1970;48:162–73.CrossRefPubMedGoogle Scholar
  43. 43.
    Kelly PT, Haponik EF. Goodpasture syndrome: Molecular and clinical advances. Medicine 1994;73:171–86.CrossRefPubMedGoogle Scholar
  44. 44.
    Shah MK, Hugghins SY. Characteristics and outcomes of patients with Goodpasture’s Syndrome. Southern Med J 2002;95:1411–8.PubMedGoogle Scholar
  45. 45.
    Briggs WA, Johnson JP, Teichman S, et al. Antiglomerular basement membrane antibody-mediated glomerulonephritis and Goodpasture’s syndrome. Medicine 1979;58:348–61.CrossRefPubMedGoogle Scholar
  46. 46.
    Teague CA, Doak PB, Simpson IJ, et al. Goodpasture’s syndrome: An analysis of 29 cases. Kidney Int 1978;13:392–504.CrossRefGoogle Scholar
  47. 47.
    Turner AN, Rees AJ. Goodpasture’s disease and Alport’s Syndrome. Annu Rev Med 1996;47:377–86.CrossRefPubMedGoogle Scholar
  48. 48.
    Young KR. Pulmonary-renal syndromes. Clin Chest Med 1989;10:655–76.PubMedGoogle Scholar
  49. 49.
    Sybers RG, Sybers JL, Dickie HA, et al. Roentgenographic aspects of hemorrhagic pulmonary-renal disease (Goodpasture’s syndrome). Am J Roentgeol 1965;94:674–80.Google Scholar
  50. 50.
    Westberg NG, Michael AF. Immunohistopathology of diabetic glomerulosclerosis. Diabetes 1972;21:163.PubMedGoogle Scholar
  51. 51.
    Alpers CE, Rennke HG, Hopper J Jr, Biava CG. Fibrillary glomerulonephritis: An entity with unusual immunofluorescence features. Kidney Int 1987;31:781.CrossRefPubMedGoogle Scholar
  52. 52.
    Lombard CM, Colby TV, Elliott CG. Surgical pathology of the lung in antibasement membrane antibody-associated Goodpasture’s syndrome. Hum Pathol 1989;20(5):445–51.CrossRefPubMedGoogle Scholar
  53. 53.
    Travis WD, et al. A clinicopathologic study of 34 cases of diffuse pulmonary hemorrhage with lung biopsy confirmation. Am J Surg Pathol 1990;14(12):1112–25.CrossRefPubMedGoogle Scholar
  54. 54.
    Beechler CR, et al. Immunofluorescence of transbronchial biopsies in Goodpasture’s syndrome. Am Rev Respir Dis 1980;121(5):869–72.PubMedGoogle Scholar
  55. 55.
    Beime GJ, et al. Immunohistology of the lung in Goodpasture’s syndrome. Ann Intern Med 1968;69(6):1207–12.Google Scholar
  56. 56.
    Leatherman JW. Immune alveolar hemorrhage. Chest 1987;91:891–7.CrossRefPubMedGoogle Scholar
  57. 57.
    Litwin CM, Mouritsen CL, Wilfahrt PA, et al. Anti-glomerular basement membrane disease: Role of enzyme-linked immunosorbent assays in diagnosis. Biochem Mol Med 1996;59:52.CrossRefPubMedGoogle Scholar
  58. 58.
    Sinico RA, Radice A, Corace C, et al. Anti-glomerular basement membrane antibodies in the diagnosis of Goodpasture syndrome: A comparison of different assays. Nephrol Dial Transplant 2006;21:397.CrossRefPubMedGoogle Scholar
  59. 59.
    Salama AD, Dougan T, Levy JB, et al. Goodpasture’s disease in the absence of circulating anti-glomerular basement membrane antibodies as detected by standard techniques. Am J Kidney Dis 2002;39:1162.CrossRefPubMedGoogle Scholar
  60. 60.
    Kalluri R, Pettrides S, Wilson CB, et al. Anti-a3[IV] collagen autoantibodies associated with lung adenocarcinoma presenting as the Goodpasture syndrome. Ann Intern Med 1996;124:651.PubMedGoogle Scholar
  61. 61.
    Charytan D, MacDonald B, Sugimoto H, et al. An unusual case of pulmonary-renal syndrome associated with defects in type IV collagen composition and anti-glomerular basement membrane autoantibodies. Am J Kidney Dis 2005;45:743.CrossRefPubMedGoogle Scholar
  62. 62.
    Jayne DR, Marshall PD, Jones SJ, Lockwood CM. Autoantibodies to GBM and neutrophil cytoplasm in rapidly progressive glomerulonephritis. Kidney Int 1990;37:965.CrossRefPubMedGoogle Scholar
  63. 63.
    O’Donoghue DJ, Short CD, Brenchley PE, et al. Sequential development of systemic vasculitis with anti-neutrophil cytoplasmic antibodies complicating anti-glomerular basement membrane disease. Clin Nephrol 1989;32:251.PubMedGoogle Scholar
  64. 64.
    Jindal KK. Management of idiopathic crescentic and diffuse proliferative glomerulonephritis: Evidence-based recommendations. Kidney Int Suppl 1999;70:S33.CrossRefGoogle Scholar
  65. 65.
    Lockwood CM, Rees AJ, Pearson TA, et al. Immunosuppression and plasma exchange in the treatment of Goodpasture’s syndrome. Lancet 1976;1:711.CrossRefPubMedGoogle Scholar
  66. 66.
    Smith PK, D’Apice JF. Plasmapheresis in rapidly progressive glomerulonephritis (editorial). Am J Med 1978;65:564.CrossRefPubMedGoogle Scholar
  67. 67.
    Johnson JP, Moore J Jr, Austin HA 3rd, Balow JE, Antonovych TT,Wilson CB. Therapy of anti-glomerular basement membrane antibody disease: Analysis of prognostic significance of clinical, pathologic and treatment factors. Medicine 1985;64:219–27.PubMedGoogle Scholar
  68. 68.
    Goranson LG, Brodin C, et al. Intravenous cyclophosphamide in patients with chronic systemic inflammatory diseases: Morbidity and mortality. Scand J Rhematol 2008 Mar–Apr;37(2):130–4.CrossRefGoogle Scholar
  69. 69.
    Weber MF, Andrassy K, Pulling O, Koderisch J, Netzer K. Antineutrophil-cytoplasmic antibodies and antiglomerular basement membrane antibodies in Goodpasture’s syndrome and in Wegener’s granulomatosis. J Am Soc Nephrol 1992;2:1227.PubMedGoogle Scholar
  70. 70.
    Maxwell AP, Nelson WE, Hill CM. Reversal of renal failure in nephritis associated with antibody to glomerular basement membrane. BMJ 1988;297:333.CrossRefPubMedGoogle Scholar
  71. 71.
    Flores JC, Taube D, Savage CO, Cameron JS, Lockwood CM, Williams DG, Ogg CS. Clinical and immunological evolution of oligoanuric anti-GBM nephritis treated by haemodialysis. Lancet 1986;1:5.CrossRefPubMedGoogle Scholar
  72. 72.
    Laczika K, Knapp S, Derfler K, et al. Immunoadsorption in Goodpasture’s syndrome. Am J Kidney Dis 2000;36:392.CrossRefPubMedGoogle Scholar
  73. 73.
    Arzoo K, Sadeghi S, Liebman HA. Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). Ann Rheum Dis 2002 Oct;61(10):922–4.CrossRefPubMedGoogle Scholar
  74. 74.
    Reynolds J, Tam FW, Chandraker A, et al. . CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis. J Clin Invest 2000;105:643.CrossRefPubMedGoogle Scholar
  75. 75.
    Reynolds J, Prodromidi EI, Juggapah JK, Abott DS, Holthaus KA, Kalluri R, Pusey CD. Nasal administration of recombinant rat alpha3[IV]NC1 prevents the development of experimental autoimmune glomerulonephritis in the WKY rat. J Am Soc Nephrol 2005 May;16(5):1350–9.CrossRefPubMedGoogle Scholar
  76. 76.
    Reynolds J, Pusey CD. Oral administration of glomerular basement membrane prevents the development of experimental autoimmune glomerulonephritis in the WKY rat. J Am Soc Nephrol 2001 Jan;12(1):61–70.PubMedGoogle Scholar
  77. 77.
    Denton MD, Singh AK. Recurrent and de novo glomerulonephritis in the renal allograft. Semin Nephrol 2000;20:164.PubMedGoogle Scholar
  78. 78.
    European best practice guidelines for renal transplantation (Part 2). Nephrol Dial Transplant 2002; 17(Suppl 4):16.Google Scholar
  79. 79.
    Floge J. Recurrent glomerulonephritis following renal transplantation: An update. Nephrol Dial Transplant 2003;18:1260.CrossRefGoogle Scholar
  80. 80.
    Knoll G, Cockfield S, Blydt-Hansen T, et al. Canadian society of transplantation consensus guidelines on eligibility for kidney transplantation. CMAJ 2005;173:1181.PubMedGoogle Scholar
  81. 81.
    Kotanko P, Pusey CD, Levy JB. Recurrent glomerulonephritis following renal transplantation. Transplantation 1997;63:1045.CrossRefPubMedGoogle Scholar
  82. 82.
    Netzer K-O, Merkel F, Weber M. Goodpasture syndrome and end-stage renal failure – to transplant or not to transplant? Nephrol Dial Transplant 1998;13:1346.PubMedGoogle Scholar
  83. 83.
    Cameron JS. Glomerulonephritis in renal transplants. Transplantation 1982;34:237.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Gangadhar Taduri
    • 1
  • Raghu Kalluri
    • 2
  • Ralph J. Panos
    • 3
  1. 1.Department of NephrologyNizam’s Institute of Medical SciencesHyderabadIndia
  2. 2.Department of Medicine, and Biological Chemistry and Molecular PharmacologyCenter for Matrix Biology, Beth Israel DeaconessBostonUSA
  3. 3.Department of Internal MedicineUniversity of Cincinnati School of Medicine and Cincinnati VA Medical CenterCincinnatiUSA

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