Anti-GBM Antibody Disease Workup
- Author: Agnieszka Swiatecka-Urban, MD; Chief Editor: Craig B Langman, MD more...
See the list below:
- Circulating anti-glomerular basement membrane (GBM) antibodies
- The presence of anti-GBM antibodies is pathognomonic.
- Detection of the anti-GBM antibodies is achieved by means of direct enzyme-linked immunoassay (ELISA). This test can be performed with less than 1 mL of blood. ELISA requires the use of native or recombinant human alpha-3 (type IV collagen) NC1 antigen as a substrate, which makes this method more sensitive and specific than others.
- The specificity of the antibody can be confirmed with Western blotting.
- False-negative rates are less than 5% and may occur in patients with low anti-GBM antibody titers or in some patients with Alport syndrome who develop anti-GBM disease after transplantation. A false-positive rate of less than 1% is related to the detection of antibodies directed against other chains of type IV collagen.
- Indirect immunofluorescent staining is rarely performed and requires an experienced renal pathologist. This test is performed by incubating normal renal tissue with the patient's serum and then treating it with fluorescein-labeled anti–IgG. Immunofluorescence indicates of immunoglobulin G (IgG) deposition and is diagnostic. False-negative results are seen in 10-40% of patients. See the image below.
- Serum electrolytes and renal function
- Renal function ranges from normal to rapidly deteriorating over a few weeks to months. Doubling of the serum creatinine level and halving of the glomerular filtration rate (GFR) within 3 months indicates rapidly progressive glomerulonephritis.
- Electrolyte abnormalities, such as hyponatremia, hyperkalemia, hyperphosphatemia, and acidemia, may be seen with advanced disease.
- Gross or microscopic hematuria may be present.
- Urinalysis may reveal nephritic urinary sediment with dysmorphic RBCs and RBC casts.
- Proteinuria is usually present, but protein levels are not in the nephrotic range.
- Blood cells
- A CBC count may reveal hypochromic microcytic anemia secondary to iron deficiency.
- Mild thrombocytopenia may be detected.
- Complements: The C3 level is below the reference range in 30-80% of pediatric patients.
- Antineutrophilic cytoplasmic antibodies (ANCA)
- ANCA are autoantibodies directed against constituents of the primary granules of neutrophils and the peroxidase positive lysosomes of monocytes.
- ANCA is detectable in as many as 30% of patients with anti-GBM disease. Titers of ANCA and anti-GBM antibodies tend to be inversely related.
- The detection of ANCA is clinically relevant in anti-GBM disease because patients with this disease are more likely to respond to therapy.
- Besides having prognostic value in anti-GBM disease, ANCA is an important diagnostic marker in the ANCA associated small-vessel vasculitis, such as Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and some forms of drug-induced vasculitis (eg, thiouracil). These conditions are included in the differential diagnosis of anti-GBM disease. Therefore, patients presenting with acute glomerulonephritis with or without pulmonary hemorrhage are routinely tested for ANCA.
- Sputum: Hemosiderin-laden macrophages indicate pulmonary hemorrhage.
See the list below:
- Renal ultrasonography usually reveals kidneys of normal size, with no anatomic abnormalities.
- When pulmonary hemorrhage is present, chest radiography may reveal alveolar infiltrates spreading from the hilum.
- Chest CT scanning is more accurate than chest radiography for the diagnosis of pulmonary hemorrhage.
See the list below:
- Results of pulmonary function tests are abnormal with pulmonary hemorrhage and may help in evaluating therapeutic effectiveness.
See the list below:
- Renal biopsy is not required for diagnosis if circulating anti-GBM antibodies are unequivocally present. However, histologic findings are an important guide to therapy and prognosis.
- Most experts recommend renal biopsy unless the procedure is contraindicated.
See the list below:
- During the active phase of the disease, cellular crescents are usually seen in the glomeruli. In advanced cases, fibrous (rather than cellular) crescents and tubulointerstitial involvement (eg, tubular atrophy, interstitial infiltrate, fibrosis) may be present. The lungs have intra-alveolar hemorrhages and are iron loaded. Vasculitis of the kidneys or lungs is uncommon but may be present in patients who are ANCA positive.
- Under immunofluorescent microscopy, the finding of linear deposition of IgG along the glomerular capillaries and, occasionally, along the tubules is nearly pathognomonic. Only 2 other renal conditions are associated with linear glomerular IgG staining: diabetic nephropathy and fibrillary glomerulonephritis. Focal and interrupted linear deposits of IgG along the alveolar basement membrane may also be seen in anti-GBM disease. Electron microscopy reveals frequent breaks of the GBM.
Kambham N. Crescentic Glomerulonephritis: An Update on Pauci-immune and Anti-GBM Diseases. Adv Anat Pathol. 2012 Mar. 19(2):111-24. [Medline].
Cui Z, Zhao MH. Advances in human antiglomerular basement membrane disease. Nat Rev Nephrol. 2011 Jul 19. 7(12):697-705. [Medline].
Ooi JD, Holdsworth SR, Kitching AR. Advances in the pathogenesis of Goodpasture's disease: from epitopes to autoantibodies to effector T cells. J Autoimmun. 2008 Nov. 31(3):295-300. [Medline].
Olson SW, Arbogast CB, Baker TP, Owshalimpur D, Oliver DK, Abbott KC, et al. Asymptomatic autoantibodies associate with future anti-glomerular basement membrane disease. J Am Soc Nephrol. 2011 Oct. 22(10):1946-52. [Medline]. [Full Text].
Wilson CB, Dixon FJ. Anti-glomerular basement membrane antibody-induced glomerulonephritis. Kidney Int. 1973 Feb. 3(2):74-89. [Medline].
Jais JP, Knebelmann B, Giatras I, et al. X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol. 2000 Apr. 11(4):649-57. [Medline].
Priest N, Roseby R, Waters E, et al. Family and carer smoking control programmes for reducing children's exposure to environmental tobacco smoke. Cochrane Database Syst Rev. 2008 Oct 8. CD001746. [Medline].
Bergs L. Goodpasture syndrome. Crit Care Nurse. 2005 Oct. 25(5):50-4, 56, 57-8. [Medline].
Bigler SA, Parry WM, Fitzwater DS, Baliga R. An 11-month-old with anti-glomerular basement membrane disease. Am J Kidney Dis. 1997 Nov. 30(5):710-2. [Medline].
Bolton WK. Goodpasture's syndrome. Kidney Int. 1996 Nov. 50(5):1753-66. [Medline].
Borza DB, Bondar O, Colon S, et al. Goodpasture autoantibodies unmask cryptic epitopes by selectively dissociatingautoantigen complexes lacking structural reinforcement: novel mechanisms for immune privilege and autoimmunepathogenesis. J Biol Chem. 2005 Jul 22. 280(29):27147-54.
Borza DB, Hudson BG. Molecular characterization of the target antigens of anti-glomerular basementmembrane antibody disease. Springer Semin Immunopathol. 2003 May. 24(4):345-61. [Medline].
Borza DB, Neilson EG, Hudson BG. Pathogenesis of Goodpasture syndrome: a molecular perspective. Semin Nephrol. 2003 Nov. 23(6):522-31. [Medline].
Boven K, Miljoen HP, Van Hoeck KJ, et al. Anti-glomerular basement membrane glomerulopathy in a young child. Pediatr Nephrol. 1996 Dec. 10(6):745-7. [Medline].
Brainwood D, Kashtan C, Gubler MC, Turner AN. Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation. Kidney Int. 1998 Mar. 53(3):762-6. [Medline]. [Full Text].
Brito MJ, Patricio A, Rolo P, et al. Anti-glomerular basement membrane nephritis in a 5-year-old girl. Pediatr Nephrol. 1997 Feb. 11(1):80-1. [Medline].
Burns AP, Fisher M, Li P, Pusey CD, Rees AJ. Molecular analysis of HLA class II genes in Goodpasture's disease. QJM. 1995 Feb. 88(2):93-100. [Medline].
Cairns LS, Phelps RG, Bowie L, Hall AM, Saweirs WW, Rees AJ. The fine specificity and cytokine profile of T-helper cells responsive to the alpha3 chain of type IV collagen in Goodpasture's disease. J Am Soc Nephrol. 2003 Nov. 14(11):2801-12. [Medline]. [Full Text].
Cole BR, Salinas-Madrigal L. Crescentic glomerulonephritis. Pediatric Nephrology. 4th ed. Baltimore, MD: Lippincott, Williams and Wilkins; 1999. 680-6.
Collard HR, Schwarz MI. Diffuse alveolar hemorrhage. Clin Chest Med. 2004 Sep. 25(3):583-92, vii.
Dean EG, Wilson GR, Li M, et al. Experimental autoimmune Goodpasture's disease: a pathogenetic role for botheffector cells and antibody in injury. Kidney Int. 2005 Feb. 67(2):566-75. [Medline].
Derk CT, Jimenez SA. Goodpasture-like syndrome induced by D-penicillamine in a patient with systemicsclerosis: report and review of the literature. J Rheumatol. 2003 Jul. 30(7):1616-20. [Medline].
Fonck C, Loute G, Cosyns JP, Pirson Y. Recurrent fulminant anti-glomerular basement membrane nephritis at a 7-year interval. Am J Kidney Dis. 1998 Aug. 32(2):323-7. [Medline].
Heeringa P, Schreiber A, Falk RJ, Jeannette JC. Pathogenesis of pulmonary vasculitis. Semin Respir Crit Care Med. 2004 Oct. 25(5):465-74. [Medline].
Hellmark T, Johansson C, Wieslander J. Characterization of anti-GBM antibodies involved in Goodpasture's syndrome. Kidney Int. 1994 Sep. 46(3):823-9. [Medline].
Hochegger K, Wolf D, Rosenkranz AR. CD4CD25 regulatory T cells: a new treatment option in glomerulonephritis. Kidney Int. 2005 Oct. 68(4):1898-9. [Medline].
Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport's syndrome, Goodpasture's syndrome, and type IV collagen. N Engl J Med. 2003 Jun 19. 348(25):2543-56. [Medline].
Jara LJ, Vera-Lastra O, Calleja MC. Pulmonary-renal vasculitic disorders: differential diagnosis and management. Curr Rheumatol Rep. 2003 Apr. 5(2):107-15. [Medline].
Kalluri R, Wilson CB, Weber M, et al. 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 Oct. 6(4):1178-85. [Medline].
Kitching AR, Holdsworth SR, Tipping PG. Crescentic glomerulonephritis--a manifestation of a nephritogenic Th1 response?. Histol Histopathol. 2000 Jul. 15(3):993-1003. [Medline].
Kotanko P, Pusey CD, Levy JB. Recurrent glomerulonephritis following renal transplantation. Transplantation. 1997 Apr 27. 63(8):1045-52. [Medline].
Laczika K, Knapp S, Derfler K, Soleiman A, Horl WH, Druml W. Immunoadsorption in Goodpasture's syndrome. Am J Kidney Dis. 2000 Aug. 36(2):392-5. [Medline].
Little MA, Pusey CD. Rapidly progressive glomerulonephritis: current and evolving treatment strategies. J Nephrol. 2004 Nov-Dec. 17 Suppl 8:S10-9.
Lou YH. Anti-GBM glomerulonephritis: a T cell-mediated autoimmune disease?. Arch Immunol Ther Exp (Warsz). 2004 Mar-Apr. 52(2):96-103. [Medline].
Madore F, Lazarus JM, Brady HR. Therapeutic plasma exchange in renal diseases [editorial]. J Am Soc Nephrol. 1996 Mar. 7(3):367-86. [Medline].
Meisels IS, Stillman IE, Kuhlik AB. Anti-glomerular basement membrane disease and dual positivity for antineutrophil cytoplasmic antibody in a patient with membranous nephropathy. Am J Kidney Dis. 1998 Oct. 32(4):646-8. [Medline].
Merkel F, Kalluri R, Marx M, et al. Autoreactive T-cells in Goodpasture's syndrome recognize the N-terminal NC1 domain on alpha 3 type IV collagen. Kidney Int. 1996 Apr. 49(4):1127-33. [Medline].
Netzer KO, Merkel F, Weber M. Goodpasture syndrome and end-stage renal failure--to transplant or not to transplant? [editorial]. Nephrol Dial Transplant. 1998 Jun. 13(6):1346-8. [Medline].
Phelps RG, Jones V, Turner AN, Rees AJ. Properties of HLA class II molecules divergently associated with Goodpasture's disease. Int Immunol. 2000 Aug. 12(8):1135-43. [Medline].
Phelps RG, Rees AJ. The HLA complex in Goodpasture's disease: a model for analyzing susceptibility to autoimmunity. Kidney Int. 1999 Nov. 56(5):1638-53. [Medline].
Reynolds J, Khan SB, Allen AR, et al. Blockade of the CD154-CD40 costimulatory pathway prevents the development of experimental autoimmune glomerulonephritis. Kidney Int. 2004 Oct. 66(4):1444-52. [Medline].
Reynolds J, Norgan VA, Bhambra U, et al. Anti-CD8 monoclonal antibody therapy is effective in the prevention and treatmentof experimental autoimmune glomerulonephritis. J Am Soc Nephrol. 2002 Feb. 13(2):359-69. [Medline].
Reynolds J, Tam FW, Chandraker A. CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis. J Clin Invest. 2000 Mar. 105(5):643-51. [Medline].
Salama AD, Chaudhry AN, Holthaus KA, et al. Regulation by CD25+ lymphocytes of autoantigen-specific T-cell responses in Goodpasture's (anti-GBM) disease. Kidney Int. 2003 Nov. 64(5):1685-94. [Medline].
Salama AD, Chaudhry AN, Holthaus KA, Mosley K, Kalluri R, Sayegh MH. Regulation by CD25+ lymphocytes of autoantigen-specific T-cell responses in Goodpasture's (anti-GBM) disease. Kidney Int. 2003 Nov. 64(5):1685-94. [Medline]. [Full Text].
Salama AD, Chaudhry AN, Ryan JJ, et al. In Goodpasture's disease, CD4(+) T cells escape thymic deletion and are reactive with the autoantigen alpha3(IV)NC1. J Am Soc Nephrol. 2001 Sep. 12(9):1908-15. [Medline].
Salama AD, Chaudhry AN, Ryan JJ, et al. In Goodpasture's disease, CD4(+) T cells escape thymic deletion and are reactive with the autoantigen alpha3(IV)NC1. J Am Soc Nephrol. 2001 Sep. 12(9):1908-15. [Medline]. [Full Text].
Salama AD, Pusey CD. Immunology of anti-glomerular basement membrane disease. Curr Opin Nephrol Hypertens. 2002 May. 11(3):279-86. [Medline].
Shah MK, Hugghins SY. Characteristics and outcomes of patients with Goodpasture's syndrome. South Med J. 2002 Dec. 95(12):1411-8. [Medline].
Srivastava A, Rao GK, Segal PE, Shah M, Geetha D. Characteristics and outcome of crescentic glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody. Clin Rheumatol. 2013 Sep. 32(9):1317-22. [Medline].
Turner AN. Antibodies: still important in anti-GBM disease. Nephron Clin Pract. 2003. 94(3):c51-2. [Medline].
Verburgh CA, Bruijn JA, Daha MR, van Es LA. Sequential development of anti-GBM nephritis and ANCA-associated Pauci- immune glomerulonephritis. Am J Kidney Dis. 1999 Aug. 34(2):344-8. [Medline].
Wang XP, Fogo AB, Colon S, Giannico G, Abul-Ezz SR, Miner JH. Distinct epitopes for anti-glomerular basement membrane alport alloantibodies and goodpasture autoantibodies within the noncollagenous domain of alpha3(IV) collagen: a janus-faced antigen. J Am Soc Nephrol. 2005 Dec. 16(12):3563-71. [Medline]. [Full Text].
Wolf D, Hochegger K, Wolf AM, et al. CD4+CD25+ regulatory T cells inhibit experimental anti-glomerular basement membrane glomerulonephritis in mice. J Am Soc Nephrol. 2005 May. 16(5):1360-70. [Medline].
Wong D, Phelps RG, Turner AN. The Goodpasture antigen is expressed in the human thymus. Kidney Int. 2001 Nov. 60(5):1777-83. [Medline].
Xenocostas A, Jothy S, Collins B, et al. Anti-glomerular basement membrane glomerulonephritis after extracorporeal shock wave lithotripsy. Am J Kidney Dis. 1999 Jan. 33(1):128-32. [Medline].
Yang R, Cui Z, Hellmark T, Segelmark M, Zhao MH, Wang HY. Natural anti-GBM antibodies from normal human sera recognize alpha3(IV)NC1 restrictively and recognize the same epitopes as anti-GBM antibodies from patients with anti-GBM disease. Clin Immunol. 2007 Aug. 124(2):207-12. [Medline]. [Full Text].
Yoshioka K, Iseki T, Okada M, Morimoto Y, Eryu N, Maki S. Identification of Goodpasture antigens in human alveolar basement membrane. Clin Exp Immunol. 1988 Dec. 74(3):419-24. [Medline].
Zou J, Henderson L, Thomas V, Swan P, Turner AN, Phelps RG. Presentation of the Goodpasture autoantigen requires proteolytic unlocking steps that destroy prominent T cell epitopes. J Am Soc Nephrol. 2007 Mar. 18(3):771-9. [Medline]. [Full Text].