Goodpasture Syndrome

Clinical Background

Goodpasture syndrome is an autoimmune condition that is characterized by rapidly progressive glomerulonephritis, pulmonary hemorrhage and antibodies to the glomerular base membrane.

Epidemiology

Incidence - less than 1/1,000,000
Age - two age peaks
- Men in late 20s
- Women and men >60 years of age
Sex - M>F
Ethnicity - Caucasians predominate

Inheritance

High prevalence of DRB1-1501 and 1502 regions haplotype is consistent with genetic predisposition to autoimmunity

Pathophysiology

Antibodies formed are directed against the alpha 3 subunit of collagen type IV (NCI domain)
Deposits of antibodies are present in the basement membrane of renal and pulmonary organs
Damage to the glomerular and alveolar basement membrane by antibodies
Three types of syndromes:
- ANCA negative
- ANCA positive (mainly myeloperoxidase antibodies)
- Post transplantation Alport syndrome (alloantibodies also to alpha 4 and alpha 5 NCI domains)

Clinical Presentation

Identification of disease often delayed since Goodpasture syndrome is not the most common cause of hemoptysis or renal failure
Pulmonary
- Pulmonary hemorrhage and hemoptysis (hemoptysis more common in smokers)
- Pulmonary involvement often precedes nephritis, the 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 weeks to acute renal failure
- Immediate treatment required to avoid irreversible kidney damage
- Acute glomerulonephritis (ususally the rapidly progressive type)
Anemia
- Pulmonary hemorrhage is the main cause of anemia
High fatality rate (75-90%) if untreated

Treatment

Cytotoxic drugs and plasma exchange are the cornerstone treatment of anti-GBM disease
- Plasmapheresis is believed to remove anti-GBM antibodies responsible for initiating damage as well as secondary circulating mediators
Remission may follow intensive plasmapheresis combined with corticosteroids and cytotoxic agents

Monitoring

Monitoring treatment
- Anti-GMB titers should decline with effective treatment
- Serum creatine levels to assess renal function
- Hemoglobin levels to monitor lung hemorrhage
Monitoring side effects of the drugs
- Surveillance for infections due to immunosuppressive drugs
- White blood cell count for drug cytotoxicity
- Platelet count for the effect of plasmapheresis

See Also

Vasculitis - ANCA

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Glomerular Basement Membrane Antibody Panel

ARUP #: 0051001

Methodology: Multi-Analyte Fluorescent Detection/Indirect Fluorescent Antibody

Use:

Detect and quantify GBM antibodies for diagnosis of Goodpasture syndrome

Limitations:

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

Follow-up:

Test name: MPO/PR-3 (ANCA) Antibodies

ARUP #: 0050707

Methodology: Multi-Analyte Fluorescent Detection

Use:

Components include the myeloperoxidase and serine protease 3 antibodies

Test name: Renal Pathology Special Studies

ARUP #: arup029

Methodology: Microscopic Exam

Use:

Confirm positive glomerular basement membrane antibody test results

Detect presence of anti-GBM antibodies in renal biopsy

Note: Request staining for anti-GBM abs and C3

Test name: CBC with Platelet Count

ARUP #: 0040002

Methodology: Automated Cell Count

Use:

Monitor anemia

Test name: Urea Nitrogen, Serum or Plasma

ARUP #: 0020023

Methodology: Spectrophotometry

Use:

Monitor renal failure

Test name: Creatinine Clearance, Urine

ARUP #: 0020474

Methodology: Spectrophotometry

Use:

Monitor renal failure

Test name: Sedimentation Rate, Westergren (ESR)

ARUP #: 0040325

Methodology: Westergren

Use:

Monitor renal failure

Additional Tests Available

Test name: Glomerular Basement Membrane Antibody, IgG by Multi-Analyte Fluorescent Detection

ARUP #: 0051000

Methodology: Multi-Analyte Fluorescent Detection

Comments:

Test name: Glomerular Basement Membrane Antibodies, IgA & IgG (IFA)

ARUP #: 0049190

Methodology: Indirect Fluorescent Antibody

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

Test name: Glomerular Basement Membrane Antibody, IgG (IFA)

ARUP #: 0049191

Methodology: Indirect Fluorescent Antibody

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

Test name: Glomerular Basement Membrane Antibody, IgA (IFA)

ARUP #: 0049192

Methodology: Indirect Fluorescent Antibody

Comments: Less specific than the quantitative tests for circulating antibodies

References

General References

Ball JA, Young KR Jr. Pulmonary manifestations of Goodpasture's syndrome. Antiglomerular basement membrane disease and related disorders. Clin Chest Med. 1998;19(4):777-91, ix.

Hatfield T, Steiger R, Wing DA. Goodpasture's disease in pregnancy: case report and review of the literature. Am J Perinatol. 2007;24(10):619-621.

Kluth DC, Rees AJ. Anti-glomerular basement membrane disease. J Am Soc Nephrol. 1999;10(11):2446-2453.

Little MA, Pusey CD. Rapidly progressive glomerulonephritis: current and evolving treatment strategies. J Nephrol. 2004;17 Suppl 8:S10-S19.

Sinclair D, Stevens JM. Role of antineutrophil cytoplasmic antibodies and glomerular basement membrane antibodies in the diagnosis and monitoring of systemic vasculitides. Ann Clin Biochem. 2007;44(Pt 5):432-442.

Troxell ML, Saxena AB, Kambham N. Concurrent anti-glomerular basement membrane disease and membranous glomerulonephritis: a case report and literature review. Clin Nephrol. 2006;66(2):120-127.

Turner N, Mason PJ, Brown R, Fox M, Povey S, Rees A, Pusey CD. Molecular cloning of the human Goodpasture antigen demonstrates it to be the alpha 3 chain of type IV collagen. J Clin Invest. 1992;89(2):592-601.

References from the ARUP Institute for Clinical and Experimental Pathology Research®

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):143-145.

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):52-56.

Medical Reviewers

Hill, Harry R., M.D. Group Medical Director, Laboratory of Immunology, ARUP Laboratories, and Executive Director of the ARUP Institute for Clinical and Experimental Pathology; Professor and Division Head, Clinical Pathology, University of Utah

Litwin, Christine, M.D. Medical Director, Immunology at ARUP Laboratories; Professor, Clinical Pathology, University of Utah

Perkins, Sherrie L. , M.D., Ph.D. Medical Director, Hematopathology at ARUP Laboratories; Professor, Anatomic Pathology, University of Utah

Tebo, Anne E., Ph.D. Assistant Medical Director, Immunology at ARUP Laboratories; Clinical Assistant Professor, Clinical Pathology, University of Utah

Comprehensive Review: July 2008
Last Update: July 2008