Antiglomerular Basement Membrane Disease - Goodpasture Syndrome

  • Diagnosis
  • Algorithms
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Pulmonary hemorrhage and/or renal disease (particularly rapid, progressive renal disease)

Laboratory Testing

  • Nonspecific testing – helpful in excluding other diagnoses or identifying organ dysfunction
    • CBC – frequently reveals anemia
    • Creatinine and blood urea nitrogen – may be elevated
    • C-reactive protein(CRP)
    • Urinalysis – hematuria common if renal involvement present
    • ANCA antibody testing
      • Moderate number of anti-GBM patients are also ANCA positive
      • Important to rule out other causes of rapidly progressive glomerulonephritis (eg, other vasculitis)
  • Glomerular basement membrane (GBM) antibody assays (serum)
    • Faster and more reliable than the less specific indirect immunofluorescent assay (IFA) test on normal kidney sections
    • Small percent of patients may have antibodies that are undetectable by current methods
    • IgG antibody to GBM antigen detected by either IFA or multiplex bead assay supports diagnosis of Goodpasture syndrome
      • Combined result of both assays (IFA and multiplex bead) performed during initial evaluation improves the diagnostic sensitivity for disease
    • A positive result in one or both assays should be confirmed by renal biopsy unless contraindicated

Histology

  • Renal biopsy
    • Useful for diagnostic confirmation and assessment of renal prognosis
    • Typical histology
      • Light microscopy – severe widespread crescentic glomerulonephritis
      • Direct immunofluorescence – linear IgG deposits in the GBM, often accompanied by C3 deposition

Differential Diagnosis

  • Monitor treatment
    • Anti-GBM antibody testing – titers should decline with effective treatment, but may not be reliable
      • Increased antibody levels following remission may be indicative of relapse
  • Monitor side effects of drugs
    • WBC count – for drug cytotoxicity
    • Platelet count – to assess the effect of plasmapheresis
    • Serum creatinine levels –  to assess renal function
    • Hemoglobin levels –  to monitor lung hemorrhage
    • Surveillance for infections due to immunosuppressive drugs

Antiglomerular basement membrane disease (Goodpasture syndrome) is an autoimmune condition characterized by rapidly progressive glomerulonephritis, pulmonary hemorrhage, and deposits of antibodies to the glomerular basement membrane (GBM).  It is categorized as a small vessel vasculitis (Chapel Hill 2012).

Epidemiology

  • Incidence – <1/million worldwide (Hellmark, 2014)
    • Accounts for 10-20% of patients presenting with acute renal failure due to rapidly progressive glomerulonephritis
      • 0.4% of children in end-stage renal disease
      • 20% of patients present with pulmonary renal syndrome
    • Very rare in pediatric population
  • Age –  2 peaks
    • 20-30 years and 50-70 years
  • Ethnicity – Caucasians predominate
  • Sex – M:F, equal

Inheritance

  • High prevalence of the DRB1*1501 and *1502 haplotypes – consistent with genetic predisposition to autoimmunity
  • Typical HLA types
    • HLA-DR15 and HLA-DR4 – positive
    • HLA-DR7 and HLA-DR1 – negative

Pathophysiology

  • Antibodies formed are directed against the noncollagenous-1 domain of type IV collagen (mainly alpha-3 chain)
  • Linear deposits of antibodies develop in the basement membrane of renal and pulmonary organs
  • Antibodies damage the glomerular and alveolar basement membrane
  • Vasculitic process involves glomerular and pulmonary capillaries

Clinical Presentation

  • Identification of disease often delayed because anti-GBM disease is an unusual cause of hemoptysis and/or renal failure (pulmonary-renal syndrome)
  • Pulmonary
    • Mild to severe disease presentation
    • Pulmonary hemorrhage and hemoptysis – hemoptysis more common in smokers
    • Pulmonary involvement often precedes nephritis – main cause of morbidity and mortality
    • Pulmonary opacities on chest radiography
    • Disease course may be dominated by recurrent hemoptysis or life-threatening pulmonary hemorrhage
  • Renal
    • Early presenting signs and symptoms – oliguria, proteinuria, hematuria
    • Renal involvement frequently progresses over a matter of days to acute renal failure
      • Acute glomerulonephritis – usually rapidly progressive type/crescentic glomerulonephritis
  • Anemia – pulmonary hemorrhage main cause of anemia
  • Pediatrics
    • Presentation more likely to be combined pulmonary/renal diseases
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Glomerular Basement Membrane Antibody, IgG by Multiplex Bead Assay and IFA 2008403
Method: Semi-Quantitative Multiplex Bead Assay/Qualitative Indirect Fluorescent Antibody

Limitations 

False-positive results may occur due to reactivity against other chains of type IV collagen 

Follow-up 

Positive result should be confirmed by renal biopsy

ANCA-Associated Vasculitis Profile (ANCA/MPO/PR-3) with Reflex to ANCA Titer 2006480
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Limitations 

Negative antibody testing does not rule out ALD

All interpretation of antibody patterns must be done in conjunction with clinical presentation; there may be overlap between diseases and antibodies detected so no single test shows absolute specificity

Renal Pathology Special Studies

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Urea Nitrogen, Serum or Plasma 0020023
Method: Quantitative Spectrophotometry

Creatinine, Serum or Plasma 0020025
Method: Quantitative Enzymatic

Limitations 

Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite) but only when concentrations are at or above those expected during acetaminophen overdose

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Guidelines

American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]

Chapter 14: Anti-glomerular basement membrane antibody glomerulonephritis Kidney Int Suppl (2011). 2012; 2(2): 240-242. PubMed

Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG M, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG I, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65(1): 1-11. PubMed

General References

Hellmark T, Segelmark M. Diagnosis and classification of Goodpasture's disease (anti-GBM). J Autoimmun. 2014; 48-49: 108-12. PubMed

Ooi JD, Holdsworth SR, Kitching R. Advances in the pathogenesis of Goodpasture's disease: from epitopes to autoantibodies to effector T cells. J Autoimmun. 2008; 31(3): 295-300. PubMed

Pedchenko V, Bondar O, Fogo AB, Vanacore R, Voziyan P, Kitching R, Wieslander J, Kashtan C, Borza D, Neilson EG, Wilson CB, Hudson BG. Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N Engl J Med. 2010; 363(4): 343-54. PubMed

Williamson SR, Phillips CL, Andreoli SP, Nailescu C. A 25-year experience with pediatric anti-glomerular basement membrane disease. Pediatr Nephrol. 2011; 26(1): 85-91. PubMed

Zhou X, Lv J, Zhao M, Zhang H. Advances in the genetics of anti-glomerular basement membrane disease. Am J Nephrol. 2010; 32(5): 482-90. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Jaskowski TD, Martins TB, Litwin CM, Hill HR. Comparison of four enzyme immunoassays for the detection of immunoglobulin G antibody against glomerular basement membrane. J Clin Lab Anal. 2002; 16(3): 143-5. PubMed

Litwin CM, Mouritsen CL, Wilfahrt PA, Schroder MC, Hill HR. Anti-glomerular basement membrane disease: role of enzyme-linked immunosorbent assays in diagnosis. Biochem Mol Med. 1996; 59(1): 52-6. PubMed

Medical Reviewers

Last Update: August 2016