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  • Review Article
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Advances in human antiglomerular basement membrane disease

Nature Reviews Nephrology volume 7, pages 697–705 (2011)Cite this article

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Abstract

Antiglomerular basement membrane (anti-GBM) disease is an autoimmune disorder that mostly presents as raised titers of antibodies against the GBM, rapidly progressive glomerulonephritis and pulmonary hemorrhage. The disease is caused by antibodies against noncollagenous domain of α3 chain of type IV collagen, which contains the epitopes EA and EB. The humoral and cellular immunity contributing to the initiation of anti-GBM disease has been extensively studied as a model for autoimmune diseases, although most of the data come from animal studies. The disease is rare, but diagnoses have been made in hundreds of patients. Substantial advances have been made in the understanding of human anti-GBM disease, and it can be treated successfully. In this Review we summarize the current knowledge on the prevalence, clinical manifestations, treatment and outcomes of human anti-GBM disease. We discuss findings on pathogenesis from human studies, with close attention to disease initiation and the immunological features of progression from quiescent autoimmune homeostasis in healthy individuals to fulminant anti-GBM disease. Further studies on autoreactive T cells are expected to clarify specific features of human anti-GBM disease and could lead to the development of new therapies.

Key Points

  • Human anti-glomerular basement membrane (anti-GBM) disease affects all races, has an annual incidence of up to 0.5–1.0 cases per million of the general population, and is strongly linked to HLA DRB1*1501

  • Although anti-GBM glomerulonephritis is rapidly progressive in most patients, cases with persistent normal renal function with mild glomerular lesions on renal biopsy have been described

  • Double positivity for autoantibodies against the GBM and antineutrophil cytoplasmic antibodies has a much worse renal prognosis than vasculitis associated with antineutrophil cytoplasmic antibodies but a similar prognosis to that seen with antibodies against the GBM alone

  • Central tolerance towards α3(IV)NC1 is incomplete and T cells and B cells specific for the autoepitopes are not deleted and/or rendered anergic

  • Changes in the immunological features of antibodies against GBM characterize progression from quiescent autoimmune homeostasis in healthy individuals to fulminant anti-GBM disease

  • Early treatment of plasmapheresis together with immunosuppression is crucial to achieve optimum overall and renal outcomes in patients with anti-GBM disease

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Figure 1: Renal biopsy findings in a patient with anti-GBM disease but normal renal function.
Figure 2: Schematic representation of cloning strategy for constructing human α3/α1 chimeric proteins and full-length human α3(IV)NC1 domain.
Figure 3: Assembly and network organization of type IV collagen protomers.

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References

  1. Stanton, M. C. & Tange, J. D. Goodpasture's syndrome (pulmonary haemorrhage associated with glomerulonephritis). Australas. Ann. Med. 7, 132–144 (1958).

    Article  CAS  PubMed  Google Scholar 

  2. Lerner, R. A., Glassock, R. J. & Dixon, F. J. The role of anti-glomerular basement membrane antibody in the pathogenesis of human glomerulonephritis. J. Exp. Med. 126, 989–1004 (1967).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sado, Y. et al. Induction of anti-GBM nephritis in rats by recombinant α3(IV)NC1 and α4(IV)NC1 of type IV collagen. Kidney Int. 53, 664–671 (1998).

    Article  CAS  PubMed  Google Scholar 

  4. Chen, L., Hellmark, T., Wieslander, J. & Bolton, W. K. Immunodominant epitopes of α3(IV)NC1 induce autoimmune glomerulonephritis in rats. Kidney Int. 64, 2108–2120 (2003).

    Article  CAS  PubMed  Google Scholar 

  5. Chen, L. et al. A nephritogenic peptide induces intermolecular epitope spreading on collagen IV in experimental autoimmune glomerulonephritis. J. Am. Soc. Nephrol. 17, 3076–3081 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Wu, J. et al. Glomerulonephritis induced by recombinant collagen IV alpha 3 chain noncollagen domain 1 is not associated with glomerular basement membrane antibody: a potential T cell-mediated mechanism. J. Immunol. 167, 2388–2395 (2001).

    Article  CAS  PubMed  Google Scholar 

  7. Robertson, J. et al. Activation of glomerular basement membrane-specific B cells in the renal draining lymph node after T cell-mediated glomerular injury. J. Am. Soc. Nephrol. 16, 3256–3263 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. Wu, J. et al. A self T cell epitope induces autoantibody response: mechanism for production of antibodies to diverse glomerular basement membrane antigens. J. Immunol. 172, 4567–4574 (2004).

    Article  CAS  PubMed  Google Scholar 

  9. Arends, J. et al. T cell epitope mimicry in antiglomerular basement membrane disease. J. Immunol. 176, 1252–1258 (2006).

    Article  CAS  PubMed  Google Scholar 

  10. Wu, J. et al. T-cell epitope of α3 chain of type IV collagen induces severe glomerulonephritis. Kidney Int. 64, 1292–1301 (2003).

    Article  CAS  PubMed  Google Scholar 

  11. Holdsworth, S. R., Kitching, A. R. & Tipping, P. G. Th1 and Th2 T helper cell subsets affect patterns of injury and outcomes in glomerulonephritis. Kidney Int. 55, 1198–1216 (1999).

    Article  CAS  PubMed  Google Scholar 

  12. Phoon, R. K. et al. T-bet deficiency attenuates renal injury in experimental crescentic glomerulonephritis. J. Am. Soc. Nephrol. 19, 477–485 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hopfer, H. et al. The importance of cell-mediated immunity in the course and severity of autoimmune anti-glomerular basement membrane disease in mice. FASAB J. 17, 860–868 (2003).

    Article  CAS  Google Scholar 

  14. Summers, S. A. et al. Th1 and Th17 cells induce proliferative glomerulonephritis. J. Am. Soc. Nephrol. 20, 2518–2524 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ooi, J. D., Phoon, R. K., Holdsworth, S. R. & Kitching, A. R. IL-23, not IL-12, directs autoimmunity to the Goodpasture antigen. J. Am. Soc. Nephrol. 20, 980–989 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yang, R. et al. Successful treatment of experimental glomerulonephritis with IdeS and EndoS, IgG-degrading streptococcal enzymes. Nephrol. Dial. Transplant. 25, 2479–2486 (2010).

    Article  CAS  PubMed  Google Scholar 

  17. Mesnard, L. et al. Invariant natural killer T cells and TGF-beta attenuate anti-GBM glomerulonephritis. J. Am. Soc. Nephrol. 20, 1282–1292 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Reynolds, J. et al. Nasal administration of recombinant rat α3(IV)NC1 prevents the development of experimental autoimmune glomerulonephritis in the WKY rat. J. Am. Soc. Nephrol. 16, 1350–1359 (2005).

    Article  CAS  PubMed  Google Scholar 

  19. Reynolds, J., Khan, S. B., Allen, A. R., Benjamin, C. D. & Pusey, C. D. Blockade of the CD154-CD40 costimulatory pathway prevents the development of experimental autoimmune glomerulonephritis. Kidney Int. 66, 1444–1452 (2004).

    Article  CAS  PubMed  Google Scholar 

  20. Duncan, D. A., Drummond, K. N., Michael, A. F. & Vernier, R. L. pulmonary hemorrhage and glomerulonephritis. report of six cases and study of the renal lesion by the fluorescent antibody technique and electron microscopy. Ann. Intern. Med. 62, 920–938 (1965).

    Article  CAS  PubMed  Google Scholar 

  21. Pusey, C. D. Anti-glomerular basement membrane disease. Kidney Int. 64, 1535–1550 (2003).

    Article  PubMed  Google Scholar 

  22. Kluth, D. C. & Rees, A. J. Anti-glomerular basement membrane disease. J. Am. Soc. Nephrol. 10, 2446–2453 (1999).

    CAS  PubMed  Google Scholar 

  23. Nachman, P. H., Jennette, J. C. & Falk, R. J. in Brenner and Rector's The Kidney 8th edn Vol. 1 Sec. V Ch. 30 (Brenner, B. M.) 1038–1042 (Saunders, Philadelphia, PA, USA, 2007).

    Google Scholar 

  24. Hirayama, K., Yamagata, K., Kobayashi, M. & Koyama, A. Anti-glomerular basement membrane antibody disease in Japan: part of the nationwide rapidly progressive glomerulonephritis survey in Japan. Clin. Exp. Nephrol. 12, 339–347 (2008).

    Article  CAS  PubMed  Google Scholar 

  25. Li, F. K. et al. Incidence and outcome of antiglomerular basement membrane disease in Chinese. Nephrology (Carlton) 9, 100–104 (2004).

    Article  Google Scholar 

  26. Cui, Z., Zhao, M. H., Xin, G. & Wang, H. Y. Characteristics and prognosis of Chinese patients with anti-glomerular basement membrane disease. Nephron Clin. Pract. 99, c49–c55 (2005).

    Article  PubMed  Google Scholar 

  27. Savage, C. O., Pusey, C. D., Bowman, C., Rees, A. J. & Lockwood, C. M. Antiglomerular basement membrane antibody mediated disease in the British Isles 1980–4. Br. Med. J. (Clin. Res. Ed.) 292, 301–304 (1986).

    Article  CAS  Google Scholar 

  28. Herody, M., Bobrie, G., Gouarin, C., Grunfeld, J. P. & Noel, L. H. Anti-GBM disease: predictive value of clinical, histological and serological data. Clin. Nephrol. 40, 249–255 (1993).

    CAS  PubMed  Google Scholar 

  29. Segelmark, M., Hellmark, T. & Wieslander, J. The prognostic significance in Goodpasture's disease of specificity, titre and affinity of anti-glomerular-basement-membrane antibodies. Nephron Clin. Pract. 94, c59–c68 (2003).

    Article  PubMed  Google Scholar 

  30. Fischer, E. G. & Lager, D. J. Anti-glomerular basement membrane glomerulonephritis: a morphologic study of 80 cases. Am. J. Clin. Pathol. 125, 445–450 (2006).

    Article  PubMed  Google Scholar 

  31. Fisher, M., Pusey, C. D., Vaughan, R. W. & Rees, A. J. Susceptibility to anti-glomerular basement membrane disease is strongly associated with HLA-DRB1 genes. Kidney Int. 51, 222–229 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Phelps, R. G. & Rees, A. J. The HLA complex in Goodpasture's disease: a model for analyzing susceptibility to autoimmunity. Kidney Int. 56, 1638–1653 (1999).

    Article  CAS  PubMed  Google Scholar 

  33. Kitagawa, W. et al. The HLA-DRB1*1501 allele is prevalent among Japanese patients with anti-glomerular basement membrane antibody-mediated disease. Nephrol. Dial. Transplant. 23, 3126–3129 (2008).

    Article  CAS  PubMed  Google Scholar 

  34. Yang, R., Cui, Z., Zhao, J. & Zhao, M. H. The role of HLA-DRB1 alleles on susceptibility of Chinese patients with anti-GBM disease. Clin. Immunol. 133, 245–250 (2009).

    Article  CAS  PubMed  Google Scholar 

  35. Appel, G. B., Radhakrishnan, J. & D'Agati, V. in Brenner and Rector's The Kidney 8th edn Vol. 1 Sec. V Ch. 31 (Brenner, B. M.) 1097–1100 (Saunders, Philadelphia, PA, USA, 2007).

    Google Scholar 

  36. Donaghy, M. & Rees, A. J. Cigarette smoking and lung haemorrhage in glomerulonephritis caused by autoantibodies to glomerular basement membrane. Lancet 2, 1390–1393 (1983).

    Article  CAS  PubMed  Google Scholar 

  37. Stevenson, A., Yaqoob, M., Mason, H., Pai, P. & Bell, G. M. Biochemical markers of basement membrane disturbances and occupational exposure to hydrocarbons and mixed solvents. QJM 88, 23–28 (1995).

    CAS  PubMed  Google Scholar 

  38. Cui, Z. et al. Concurrent antiglomerular basement membrane disease and immune complex glomerulonephritis. Ren. Fail. 28, 7–14 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. Hellmark, T., Niles, J. L., Collins, A. B., McCluskey, R. T. & Brunmark, C. Comparison of anti-GBM antibodies in sera with or without ANCA. J. Am. Soc. Nephrol. 8, 376–385 (1997).

    CAS  PubMed  Google Scholar 

  40. Levy, J. B., Hammad, T., Coulthart, A., Dougan, T. & Pusey, C. D. Clinical features and outcome of patients with both ANCA and anti-GBM antibodies. Kidney Int. 66, 1535–1540 (2004).

    Article  CAS  PubMed  Google Scholar 

  41. Zhao, J. et al. Characteristics and outcome of Chinese patients with both antineutrophil cytoplasmic antibody and antiglomerular basement membrane antibodies. Nephron Clin. Pract. 107, c56–c62 (2007).

    Article  CAS  PubMed  Google Scholar 

  42. Rutgers, A. et al. Coexistence of anti-glomerular basement membrane antibodies and myeloperoxidase-ANCAs in crescentic glomerulonephritis. Am. J. Kidney Dis. 46, 253–262 (2005).

    Article  PubMed  Google Scholar 

  43. O'Connor, K., Fulcher, D. & Phoon, R. K. Development of anti-glomerular basement membrane disease after remission from perinuclear ANCA-associated glomerulonephritis in a patient with HLA susceptibility. Am. J. Kidney Dis. 55, 566–569 (2010).

    Article  PubMed  Google Scholar 

  44. Wilson, C. B. & Dixon, F. J. Anti-glomerular basement membrane antibody-induced glomerulonephritis. Kidney Int. 3, 74–89 (1973).

    Article  CAS  PubMed  Google Scholar 

  45. Lin, W., Chen, M., Cui, Z. & Zhao, M. H. The immunopathological spectrum of crescentic glomerulonephritis: a survey of 106 patients in a single Chinese center. Nephron Clin. Pract. 116, c65–c74 (2010).

    Article  PubMed  Google Scholar 

  46. Couser, W. G. Rapidly progressive glomerulonephritis: classification, pathogenetic mechanisms, and therapy. Am. J. Kidney Dis. 11, 449–464 (1988).

    Article  CAS  PubMed  Google Scholar 

  47. Cui, Z., Zhao, J., Jia, X. Y., Zhu, S. N. & Zhao, M. H. Clinical features and outcomes of anti-glomerular basement membrane disease in older patients. Am. J. Kidney Dis. 57, 575–582 (2011).

    Article  PubMed  Google Scholar 

  48. Ang, C. et al. Anti-glomerular basement membrane (GBM)-antibody-mediated disease with normal renal function. Nephrol. Dial. Transplant. 13, 935–939 (1998).

    Article  CAS  PubMed  Google Scholar 

  49. Cui, Z., Zhao, M. H., Singh, A. K. & Wang, H. Y. Antiglomerular basement membrane disease with normal renal function. Kidney Int. 72, 1403–1408 (2007).

    Article  CAS  PubMed  Google Scholar 

  50. Ewan, P. W., Jones, H. A., Rhodes, C. G. & Hughes, J. M. Detection of intrapulmonary hemorrhage with carbon monoxide uptake. Application in goodpasture's syndrome. N. Engl. J. Med. 295, 1391–1396 (1976).

    Article  CAS  PubMed  Google Scholar 

  51. Cui, Z. et al. Outcomes of Chinese patients with anti-glomerular basement membrane disease receiving different therapeutic regimens: a large cohort study from a single center. Medicine (Baltimore) (in press).

  52. Sinico, R. A., Radice, A., Corace, C., Sabadini, E. & Bollini, B. Anti-glomerular basement membrane antibodies in the diagnosis of Goodpasture syndrome: a comparison of different assays. Nephrol. Dial. Transplant. 21, 397–401 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Salama, A. D. et al. Goodpasture's disease in the absence of circulating anti-glomerular basement membrane antibodies as detected by standard techniques. Am. J. Kidney Dis. 39, 1162–1167 (2002).

    Article  PubMed  Google Scholar 

  54. Hudson, B. G., Tryggvason, K., Sundaramoorthy, M. & Neilson, E. G. Alport's syndrome, Goodpasture's syndrome, and type IV collagen. N. Engl. J. Med. 348, 2543–2556 (2003).

    Article  CAS  PubMed  Google Scholar 

  55. Abrahamson, D. R., Hudson, B. G., Stroganova, L., Borza, D. B. & St John, P. L. Cellular origins of type IV collagen networks in developing glomeruli. J. Am. Soc. Nephrol. 20, 1471–1479 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Borza, D. B. et al. Goodpasture autoantibodies unmask cryptic epitopes by selectively dissociating autoantigen complexes lacking structural reinforcement: novel mechanisms for immune privilege and autoimmune pathogenesis. J. Biol. Chem. 280, 27147–27154 (2005).

    Article  CAS  PubMed  Google Scholar 

  57. Vanacore, R. M. et al. A role for collagen IV cross-links in conferring immune privilege to the Goodpasture autoantigen: structural basis for the crypticity of B cell epitopes. J. Biol. Chem. 283, 22737–22748 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Vanacore, R. et al. A sulfilimine bond identified in collagen IV. Science 325, 1230–1234 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Yoshioka, K. et al. Identification of Goodpasture antigens in human alveolar basement membrane. Clin. Exp. Immunol. 74, 419–424 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Kalluri, R. et al. Identification of the α3 chain of type IV collagen as the common autoantigen in antibasement membrane disease and Goodpasture syndrome. J. Am. Soc. Nephrol. 6, 1178–1185 (1995).

    CAS  PubMed  Google Scholar 

  61. Saus, J., Wieslander, J., Langeveld, J. P., Quinones, S. & Hudson, B. G. Identification of the Goodpasture antigen as the α3(IV) chain of collagen IV. J. Biol. Chem. 263, 13374–13380 (1988).

    CAS  PubMed  Google Scholar 

  62. Pedchenko, V. et al. Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N. Engl. J. Med. 363, 343–354 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Netzer, K. O. et al. The goodpasture autoantigen. Mapping the major conformational epitope(s) of α3(IV) collagen to residues 17–31 and 127–141 of the NC1 domain. J. Biol. Chem. 274, 11267–11274 (1999).

    Article  CAS  PubMed  Google Scholar 

  64. Borza, D. B. et al. Quaternary organization of the goodpasture autoantigen, the α3(IV) collagen chain. Sequestration of two cryptic autoepitopes by intrapromoter interactions with the α4 and α5 NC1 domains. J. Biol. Chem. 277, 40075–40083 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. David, M., Borza, D. B., Leinonen, A., Belmont, J. M. & Hudson, B. G. Hydrophobic amino acid residues are critical for the immunodominant epitope of the Goodpasture autoantigen. A molecular basis for the cryptic nature of the epitope. J. Biol. Chem. 276, 6370–6377 (2001).

    Article  CAS  PubMed  Google Scholar 

  66. Kalluri, R., Cantley, L. G., Kerjaschki, D. & Neilson, E. G. Reactive oxygen species expose cryptic epitopes associated with autoimmune goodpasture syndrome. J. Biol. Chem. 275, 20027–20032 (2000).

    Article  CAS  PubMed  Google Scholar 

  67. Ghohestani, R. F. et al. Crescentic glomerulonephritis and subepidermal blisters with autoantibodies to alpha5 and alpha6 chains of type IV collagen. Lab. Invest. 83, 605–611 (2003).

    Article  CAS  PubMed  Google Scholar 

  68. Ghohestani, R. F., Hudson, B. G., Claudy, A. & Uitto, J. The α5 chain of type IV collagen is the target of IgG autoantibodies in a novel autoimmune disease with subepidermal blisters and renal insufficiency. J. Biol. Chem. 275, 16002–16006 (2000).

    Article  CAS  PubMed  Google Scholar 

  69. Kalluri, R. et al. Anti-α1(IV) collagen autoantibodies associated with lung adenocarcinoma presenting as the Goodpasture syndrome. Ann. Intern. Med. 124, 651–653 (1996).

    Article  CAS  PubMed  Google Scholar 

  70. Zhao, J. et al. Anti-glomerular basement membrane autoantibodies against different target antigens are associated with disease severity. Kidney Int. 76, 1108–1115 (2009).

    Article  CAS  PubMed  Google Scholar 

  71. Yang, R. et al. Antigen and epitope specificity of anti-glomerular basement membrane antibodies in patients with goodpasture disease with or without anti-neutrophil cytoplasmic antibodies. J. Am. Soc. Nephrol. 18, 1338–1343 (2007).

    Article  CAS  PubMed  Google Scholar 

  72. Dehan, P. et al. Sera from patients with anti-GBM nephritis including goodpasture syndrome show heterogenous reactivity to recombinant NC1 domain of type IV collagen α chains. Nephrol. Dial. Transplant. 11, 2215–2222 (1996).

    Article  CAS  PubMed  Google Scholar 

  73. Hellmark, T., Johansson, C. & Wieslander, J. Characterization of anti-GBM antibodies involved in Goodpasture's syndrome. Kidney Int. 46, 823–829 (1994).

    Article  CAS  PubMed  Google Scholar 

  74. Johansson, C., Butkowski, R., Swedenborg, P., Alm, P. & Wieslander, J. Characterization of a non-Goodpasture autoantibody to type IV collagen. Nephrol. Dial. Transplant. 8, 1205–1210 (1993).

    CAS  PubMed  Google Scholar 

  75. Hellmark, T. et al. Identification of a clinically relevant immunodominant region of collagen IV in Goodpasture disease. Kidney Int. 55, 936–944 (1999).

    Article  CAS  PubMed  Google Scholar 

  76. Yang, R. et al. Levels of epitope-specific autoantibodies correlate with renal damage in anti-GBM disease. Nephrol. Dial. Transplant. 24, 1838–1844 (2009).

    Article  CAS  PubMed  Google Scholar 

  77. Levy, J. B., Turner, A. N., Rees, A. J. & Pusey, C. D. Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression. Ann. Intern. Med. 134, 1033–1042 (2001).

    Article  CAS  PubMed  Google Scholar 

  78. Jindal, K. K. Management of idiopathic crescentic and diffuse proliferative glomerulonephritis: evidence-based recommendations. Kidney Int. Suppl. 70, S33–40 (1999).

    Article  CAS  PubMed  Google Scholar 

  79. Lockwood, C. M., Boulton-Jones, J. M., Lowenthal, R. M., Simpson, I. J. & Peters, D. K. Recovery from Goodpasture's syndrome after immunosuppressive treatment and plasmapheresis. Br. Med. J. 2, 252–254 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Cui, Z., Wang, H. Y. & Zhao, M. H. Natural autoantibodies against glomerular basement membrane exist in normal human sera. Kidney Int. 69, 894–899 (2006).

    Article  CAS  PubMed  Google Scholar 

  81. Coutinho, A., Kazatchkine, M. D. & Avrameas, S. Natural autoantibodies. Curr. Opin. Immunol. 7, 812–818 (1995).

    Article  CAS  PubMed  Google Scholar 

  82. Hayakawa, K. et al. Positive selection of natural autoreactive B cells. Science 285, 113–116 (1999).

    Article  CAS  PubMed  Google Scholar 

  83. Kazatchkine, M. D. & Kaveri, S. V. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N. Engl. J. Med. 345, 747–755 (2001).

    Article  CAS  PubMed  Google Scholar 

  84. Yang, R. et al. Natural anti-GBM antibodies from normal human sera recognize α3(IV)NC1 restrictively and recognize the same epitopes as anti-GBM antibodies from patients with anti-GBM disease. Clin. Immunol. 124, 207–212 (2007).

    Article  CAS  PubMed  Google Scholar 

  85. Salama, A. D., Levy, J. B., Lightstone, L. & Pusey, C. D. Goodpasture's disease. Lancet 358, 917–920 (2001).

    Article  CAS  PubMed  Google Scholar 

  86. Cui, Z. & Zhao, M. H. Avidity of anti-glomerular basement membrane autoantibodies was associated with disease severity. Clin. Immunol. 116, 77–82 (2005).

    Article  CAS  PubMed  Google Scholar 

  87. Rutgers, A. et al. High affinity of anti-GBM antibodies from Goodpasture and transplanted Alport patients to α3(IV)NC1 collagen. Kidney Int. 58, 115–122 (2000).

    Article  CAS  PubMed  Google Scholar 

  88. Zhao, J., Yan, Y., Cui, Z., Yang, R. & Zhao, M. H. The immunoglobulin G subclass distribution of anti-GBM autoantibodies against rHα3(IV)NC1 is associated with disease severity. Hum. Immunol. 70, 425–429 (2009).

    Article  CAS  PubMed  Google Scholar 

  89. Cui, Z., Zhao, M. H., Segelmark, M. & Hellmark, T. Natural autoantibodies to myeloperoxidase, proteinase 3, and the glomerular basement membrane are present in normal individuals. Kidney Int. 78, 590–597 (2010).

    Article  CAS  PubMed  Google Scholar 

  90. Wong, D., Phelps, R. G. & Turner, A. N. The Goodpasture antigen is expressed in the human thymus. Kidney Int. 60, 1777–1783 (2001).

    Article  CAS  PubMed  Google Scholar 

  91. Zou, J. et al. Healthy individuals have Goodpasture autoantigen-reactive T cells. J. Am. Soc. Nephrol. 19, 396–404 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Salama, A. D. et al. In Goodpasture's disease, CD4+ T cells escape thymic deletion and are reactive with the autoantigen α3(IV)NC1. J. Am. Soc. Nephrol. 12, 1908–1915 (2001).

    CAS  PubMed  Google Scholar 

  93. Salama, A. D. et al. Regulation by CD25+ lymphocytes of autoantigen-specific T-cell responses in Goodpasture's (anti-GBM) disease. Kidney Int. 64, 1685–1694 (2003).

    Article  CAS  PubMed  Google Scholar 

  94. Nolasco, F. E. et al. Intraglomerular T cells and monocytes in nephritis: study with monoclonal antibodies. Kidney Int. 31, 1160–1166 (1987).

    Article  CAS  PubMed  Google Scholar 

  95. Hellmark, T., Brunmark, C., Trojnar, J. & Wieslander, J. Epitope mapping of anti-glomerular basement membrane (GBM) antibodies with synthetic peptides. Clin. Exp. Immunol. 105, 504–510 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Cairns, L. S. et al. The fine specificity and cytokine profile of T-helper cells responsive to the α3 chain of type IV collagen in Goodpasture's disease. J. Am. Soc. Nephrol. 14, 2801–2812 (2003).

    Article  CAS  PubMed  Google Scholar 

  97. Zou, J. et al. Presentation of the Goodpasture autoantigen requires proteolytic unlocking steps that destroy prominent T cell epitopes. J. Am. Soc. Nephrol. 18, 771–779 (2007).

    Article  CAS  PubMed  Google Scholar 

  98. Johnson, J. P., Whitman, W., Briggs, W. A. & Wilson, C. B. Plasmapheresis and immunosuppressive agents in antibasement membrane antibody-induced Goodpasture's syndrome. Am. J. Med. 64, 354–359 (1978).

    Article  CAS  PubMed  Google Scholar 

  99. Lionaki, S., Jennette, J. C. & Falk, R. J. Anti-neutrophil cytoplasmic (ANCA) and anti-glomerular basement membrane (GBM) autoantibodies in necrotizing and crescentic glomerulonephritis. Semin. Immunopathol. 29, 459–474 (2007).

    Article  CAS  PubMed  Google Scholar 

  100. Kelly, P. T. & Haponik, E. F. Goodpasture syndrome: molecular and clinical advances. Medicine (Baltimore) 73, 171–185 (1994).

    Article  CAS  Google Scholar 

  101. Daly, C., Conlon, P. J., Medwar, W. & Walshe, J. J. Characteristics and outcome of anti-glomerular basement membrane disease: a single-center experience. Ren. Fail. 18, 105–112 (1996).

    Article  CAS  PubMed  Google Scholar 

  102. Merkel, F., Pullig, O., Marx, M., Netzer, K. O. & Weber, M. Course and prognosis of anti-basement membrane antibody (anti-BM-Ab)-mediated disease: report of 35 cases. Nephrol. Dial. Transplant. 9, 372–376 (1994).

    CAS  PubMed  Google Scholar 

  103. Johnson, J. P. et al. Therapy of anti-glomerular basement membrane antibody disease: analysis of prognostic significance of clinical, pathologic and treatment factors. Medicine (Baltimore) 64, 219–227 (1985).

    Article  CAS  Google Scholar 

  104. Bell, D. D., Moffatt, S. L., Singer, M. & Munt, P. W. Antibasement membrane antibody disease without clinical evidence of renal disease. Am. Rev. Respir. Dis. 142, 234–237 (1990).

    Article  CAS  PubMed  Google Scholar 

  105. Zimmerman, S. W., Varanasi, U. R. & Hoff, B. Goodpasture's syndrome with normal renal function. Am. J. Med. 66, 163–171 (1979).

    Article  CAS  PubMed  Google Scholar 

  106. Min, S. A. et al. Goodpasture's syndrome with normal renal function. Nephrol. Dial. Transplant. 11, 2302–2305 (1996).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors' work is supported by a grant from Natural Science Fund of China to the Innovation Research Group (81021004).

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  1. Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, 100034, China

    Zhao Cui & Ming-Hui Zhao

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  1. Zhao Cui
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  2. Ming-Hui Zhao
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Both authors contributed equally to researching data, discussing content, writing, and reviewing/editing this article before submission.

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Correspondence to Ming-Hui Zhao.

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Cui, Z., Zhao, MH. Advances in human antiglomerular basement membrane disease. Nat Rev Nephrol 7, 697–705 (2011). https://doi.org/10.1038/nrneph.2011.89

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