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Anti-GBM antibody disease: Recurrence after transplantation

Authors
Daniel C Brennan, MD, FACP
Andrew Malone, MB, BCh, MRCPI
Section Editor
Barbara Murphy, MB, BAO, BCh, FRCPI
Deputy Editor
Albert Q Lam, MD

INTRODUCTION

Anti-glomerular basement membrane (GBM) antibody disease may progress to end-stage renal failure, requiring either dialysis or renal transplantation. The incidence of recurrent linear immunoglobulin G (IgG) staining in the transplant may be as high as 50 percent [1,2]. However, most patients remain asymptomatic [1].

There are only six reported cases of symptomatic recurrent anti-GBM disease in the literature [3]. A related phenomenon is the development of de novo anti-GBM disease in patients with Alport syndrome (also known as Alport posttransplant anti-GBM nephritis), which can lead to graft loss in up to 5 percent of recipients [4].

This topic reviews recurrent anti-GBM disease after transplantation. The pathogenesis, diagnosis, and treatment of anti-GBM disease are discussed elsewhere. (See "Pathogenesis and diagnosis of anti-GBM antibody (Goodpasture's) disease" and "Treatment of anti-GBM antibody (Goodpasture's) disease".)

De novo anti-GBM disease following transplantation in patients with Alport syndrome is also discussed elsewhere. (See "Clinical manifestations, diagnosis, and treatment of Alport syndrome (hereditary nephritis)", section on 'Anti-GBM antibody disease'.)

PATHOGENESIS

The target glomerular basement membrane (GBM) antigens for recurrent anti-GBM disease are the noncollagenous-1 (NC1) domains of the alpha-3 and alpha-5 chains of collagen IV (alpha3[IV]NC1 and alpha5[IV]NC1) [5-8]. Collagen IV is a family of six alpha chains (alpha-1 through alpha-6) [9]. The alpha-3, alpha-4, and alpha-5 chains form a triple helical protomer, and oligomerization of alpha-345 protomers, by means of NC1-NC1 end-to-end associations, forms the hexameric NC1 domain.

   
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Literature review current through: Nov 2017. | This topic last updated: Jun 13, 2017.
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References
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  1. Kotanko P, Pusey CD, Levy JB. Recurrent glomerulonephritis following renal transplantation. Transplantation 1997; 63:1045.
  2. McAdoo SP, Pusey CD. Anti-Glomerular Basement Membrane Disease. Clin J Am Soc Nephrol 2017; 12:1162.
  3. Sauter M, Schmid H, Anders HJ, et al. Loss of a renal graft due to recurrence of anti-GBM disease despite rituximab therapy. Clin Transplant 2009; 23:132.
  4. Kashtan CE. Renal transplantation in patients with Alport syndrome. Pediatr Transplant 2006; 10:651.
  5. Saus J, Wieslander J, Langeveld JP, et al. Identification of the Goodpasture antigen as the alpha 3(IV) chain of collagen IV. J Biol Chem 1988; 263:13374.
  6. Butkowski RJ, Langeveld JP, Wieslander J, et al. Localization of the Goodpasture epitope to a novel chain of basement membrane collagen. J Biol Chem 1987; 262:7874.
  7. Turner N, Mason PJ, Brown R, et al. Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha 3 chain of type IV collagen. J Clin Invest 1992; 89:592.
  8. Pedchenko V, Bondar O, Fogo AB, et al. Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N Engl J Med 2010; 363:343.
  9. 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.
  10. Hudson BG, Kalluri R, Gunwar S, et al. The pathogenesis of Alport syndrome involves type IV collagen molecules containing the alpha 3(IV) chain: evidence from anti-GBM nephritis after renal transplantation. Kidney Int 1992; 42:179.
  11. Kang JS, Kashtan CE, Turner AN, et al. The alloantigenic sites of alpha3alpha4alpha5(IV) collagen: pathogenic X-linked alport alloantibodies target two accessible conformational epitopes in the alpha5NC1 domain. J Biol Chem 2007; 282:10670.
  12. Border WA, Baehler RW, Bhathena D, Glassock RJ. IgA antibasement membrane nephritis with pulmonary hemorrhage. Ann Intern Med 1979; 91:21.
  13. Shaer AJ, Stewart LR, Cheek DE, et al. IgA antiglomerular basement membrane nephritis associated with Crohn's disease: a case report and review of glomerulonephritis in inflammatory bowel disease. Am J Kidney Dis 2003; 41:1097.
  14. Maes B, Vanwalleghem J, Kuypers D, et al. IgA antiglomerular basement membrane disease associated with bronchial carcinoma and monoclonal gammopathy. Am J Kidney Dis 1999; 33:E3.
  15. Gris P, Pirson Y, Hamels J, et al. Antiglomerular basement membrane nephritis induced by IgA1 antibodies. Nephron 1991; 58:418.
  16. Fervenza FC, Terreros D, Boutaud A, et al. Recurrent Goodpasture's disease due to a monoclonal IgA-kappa circulating antibody. Am J Kidney Dis 1999; 34:549.
  17. Borza DB, Chedid MF, Colon S, et al. Recurrent Goodpasture's disease secondary to a monoclonal IgA1-kappa antibody autoreactive with the alpha1/alpha2 chains of type IV collagen. Am J Kidney Dis 2005; 45:397.
  18. Denton MD, Singh AK. Recurrent and de novo glomerulonephritis in the renal allograft. Semin Nephrol 2000; 20:164.
  19. EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.2.5. Chronic graft dysfunction. Late recurrence of primary glomerulonephritides. Nephrol Dial Transplant 2002; 17 Suppl 4:16.
  20. Floege J. Recurrent glomerulonephritis following renal transplantation: an update. Nephrol Dial Transplant 2003; 18:1260.
  21. Knoll G, Cockfield S, Blydt-Hansen T, et al. Canadian Society of Transplantation consensus guidelines on eligibility for kidney transplantation. CMAJ 2005; 173:1181.
  22. Netzer KO, Merkel F, Weber M. Goodpasture syndrome and end-stage renal failure--to transplant or not to transplant? Nephrol Dial Transplant 1998; 13:1346.
  23. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009; 9 Suppl 3:S1.