Goodpasture Syndrome - Anti-GBM Disease

Diagnosis

Indications for Testing

  • Patient presenting with pulmonary hemorrhage and renal disease

Laboratory Testing

  • Serum glomerular basement membrane (GBM) antibody assays
    • Faster and more reliable than the less specific indirect immunofluorescent test on normal kidney sections
    • 2-3% of patients may have antibodies that are undetectable by current methods
  • ANCA antibody testing
    • Approximately 30% of anti-GBM positive samples are also ANCA positive
    • Rule out other causes of rapidly progressive glomerulonephritis
  • Nonspecific testing
    • CBC – frequently reveals anemia
    • Creatinine and blood urea nitrogen – may be elevated
    • Erythrocyte sedimentation rate – usually elevated
    • Urinalysis – may detect hematuria

Histology

  • Renal biopsy
    • Diagnostic confirmation and assessment of renal prognosis
    • Severe crescentic glomerulonephritis – linear IgG deposits in the GBM

Differential Diagnosis

Monitoring

  • 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

Clinical Background

Goodpasture syndrome is an autoimmune condition characterized by rapidly progressive glomerulonephritis, pulmonary hemorrhage, and deposits of antibodies to the glomerular basement membrane (GBM). In anti-GBM disease, 45% of cases show kidney and pulmonary involvement (Goodpasture syndrome), 5% of cases have isolated lung involvement, and 50% of cases involve only the kidney.

Epidemiology

  • Incidence – 1-2/1,000,000
    • 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 – male predominance
    • 50-70 years – female predominance
  • Ethnicity – Caucasians predominate

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 (NC-1) domain of type IV collagen – mainly alpha-3 (IV) chain
  • Linear deposits of antibodies develop in the basement membrane of renal and pulmonary organs
  • Antibodies damage the glomerular and alveolar basement membrane

Clinical Presentation

  • Identification of disease often delayed because Goodpasture syndrome is not the most common cause of hemoptysis or renal failure (pulmonary-renal syndrome)
  • Pulmonary
    • 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
      • Immediate treatment required to avoid irreversible kidney damage
    • Acute glomerulonephritis – usually rapidly progressive type/crescentic glomerulonephritis
  • Anemia – pulmonary hemorrhage main cause of anemia
  • Outcomes
    • Untreated – universally poor outcome
    • With treatment, no dialysis, and creatinine <6 mg/dL at one year – patient (83%) and patient's kidney (82%) survival rates
    • With dialysis at one year – patient (65%) and patient's kidney (8%) survival rates

Treatment

  • Early diagnosis and treatment correlates with better outcome
  • Cytotoxic drugs and plasma exchange – cornerstone treatment of anti-GBM disease
    • Plasmapheresis believed to remove anti-GBM antibodies responsible for initiating damage as well as secondary circulating mediators
  • Remission may follow intensive plasmapheresis treatment combined with corticosteroids and cytotoxic agents

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
Glomerular Basement Membrane Antibody, IgG by Multiplex Bead Assay and IFA 2008403
Method: Semi-Quantitative Multiplex Bead Assay/Qualitative Indirect Fluorescent Antibody

Detect and quantify glomerular base membrane (GBM) antibodies for diagnosis of Goodpasture syndrome

Panel includes GBM antibodies IgG

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

2-3% may have antibodies undetectable by current methods

 
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

Rule out other causes of glomerulonephritis

Components include myeloperoxidase and serine protease 3 antibodies

   
Renal Pathology Special Studies

Confirm positive GBM antibody results

Detect presence of anti-GBM antibodies in renal biopsy

Note: Request staining for anti-GBM antibodies and C3

   
CBC with Platelet Count 0040002
Method: Automated Cell Count

Evaluate for anemia in anti-GBM disease

Monitor side effects of immunosuppressive agents in Goodpasture syndrome

   
Urea Nitrogen, Serum or Plasma 0020023
Method: Quantitative Spectrophotometry

Aid in diagnosis of renal involvement in anti-GBM disease

Monitor renal failure

   
Creatinine, Serum or Plasma 0020025
Method: Quantitative Enzymatic

Aid in diagnosis of renal involvement in anti-GBM disease

Monitor renal failure

   
Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Evaluate for presence of hematuria, proteinuria in anti-GBM disease

   
Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Assess degree of inflammation in anti-GBM disease

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Glomerular Basement Membrane Antibody, IgG by Multiplex Bead Assay 0051000
Method: Semi-Quantitative Multiplex Bead Assay
Glomerular Basement Membrane Antibody, IgG (IFA) 0049191
Method: Indirect Fluorescent Antibody

Less specific than the quantitative tests for circulating antibodies; all positive results need to be confirmed by semi-quantitative tests and/or renal biopsy