Abstract
Goodpasture's disease, or anti-glomerular basement membrane (anti-GBM) disease, is a systemic autoimmune disorder defined by anti-GBM antibody-mediated damage (mainly immunoglobulin G-1) resulting in progressive crescentic glomerulonephritis and, frequently, diffuse pulmonary alveolar hemorrhage. It may be regarded as a "conformeropathy" where the quaternary structure of the α345NC1 hexamer that constitutes GBM undergoes a conformational change, exposing pathogenic epitopes on the α3 and α5 chains, eliciting a pathogenic autoantibody anti-GBM response. Goodpasture's disease accounts for 20% of all patients presenting with a pulmonary-renal syndrome and may be associated with detectable perinuclear antineutrophil cytoplasmic autoantibody positivity in up to a third of patients. Associated triggers may include tobacco smoking, hydrocarbon solvent exposure, and cocaine abuse. Cough, hemoptysis, and dyspnea with fatigue are the commonest presenting features. It is critical to rapidly distinguish Goodpasture's disease from other causes of pulmonary-renal syndromes such as Wegener's granulomatosis. Early and intensive treatment with plasmapheresis and immunosuppression with systemic corticosteroids pending results of diagnostic testing, and later cyclophosphamide, is often beneficial, with 90% of patients surviving the acute presentation of Goodpasture's disease. The need for hemodialysis on initial presentation, a serum creatinine >5 mg/dL, and 50% to 100% crescents on renal biopsy, portend the necessity of long-term hemodialysis. Further elucidation of the molecular pathobiology of Goodpasture's disease, particularly the regulation of involved antigen-specific T cells, may improve early diagnosis, treatment, and outcomes in this rare but potentially lethal autoimmune disorder.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 151-162 |
| Number of pages | 12 |
| Journal | Clinical Reviews in Allergy and Immunology |
| Volume | 41 |
| Issue number | 2 |
| DOIs | |
| State | Published - Oct 2011 |
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Keywords
- Alveolar hemorrhage
- Anti-GBM
- Antibodies
- Glomerulonephritis
- Goodpasture's
- Plasmapheresis
ASJC Scopus subject areas
- Immunology and Allergy
Cite this
Cutting edge issues in Goodpasture's disease. / Chan, Andrew; Louie, Samuel; Leslie, Kevin O.; Juarez, Maya M.; Albertson, Timothy E.
In: Clinical Reviews in Allergy and Immunology, Vol. 41, No. 2, 10.2011, p. 151-162.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cutting edge issues in Goodpasture's disease
AU - Chan, Andrew
AU - Louie, Samuel
AU - Leslie, Kevin O.
AU - Juarez, Maya M.
AU - Albertson, Timothy E
PY - 2011/10
Y1 - 2011/10
N2 - Goodpasture's disease, or anti-glomerular basement membrane (anti-GBM) disease, is a systemic autoimmune disorder defined by anti-GBM antibody-mediated damage (mainly immunoglobulin G-1) resulting in progressive crescentic glomerulonephritis and, frequently, diffuse pulmonary alveolar hemorrhage. It may be regarded as a "conformeropathy" where the quaternary structure of the α345NC1 hexamer that constitutes GBM undergoes a conformational change, exposing pathogenic epitopes on the α3 and α5 chains, eliciting a pathogenic autoantibody anti-GBM response. Goodpasture's disease accounts for 20% of all patients presenting with a pulmonary-renal syndrome and may be associated with detectable perinuclear antineutrophil cytoplasmic autoantibody positivity in up to a third of patients. Associated triggers may include tobacco smoking, hydrocarbon solvent exposure, and cocaine abuse. Cough, hemoptysis, and dyspnea with fatigue are the commonest presenting features. It is critical to rapidly distinguish Goodpasture's disease from other causes of pulmonary-renal syndromes such as Wegener's granulomatosis. Early and intensive treatment with plasmapheresis and immunosuppression with systemic corticosteroids pending results of diagnostic testing, and later cyclophosphamide, is often beneficial, with 90% of patients surviving the acute presentation of Goodpasture's disease. The need for hemodialysis on initial presentation, a serum creatinine >5 mg/dL, and 50% to 100% crescents on renal biopsy, portend the necessity of long-term hemodialysis. Further elucidation of the molecular pathobiology of Goodpasture's disease, particularly the regulation of involved antigen-specific T cells, may improve early diagnosis, treatment, and outcomes in this rare but potentially lethal autoimmune disorder.
AB - Goodpasture's disease, or anti-glomerular basement membrane (anti-GBM) disease, is a systemic autoimmune disorder defined by anti-GBM antibody-mediated damage (mainly immunoglobulin G-1) resulting in progressive crescentic glomerulonephritis and, frequently, diffuse pulmonary alveolar hemorrhage. It may be regarded as a "conformeropathy" where the quaternary structure of the α345NC1 hexamer that constitutes GBM undergoes a conformational change, exposing pathogenic epitopes on the α3 and α5 chains, eliciting a pathogenic autoantibody anti-GBM response. Goodpasture's disease accounts for 20% of all patients presenting with a pulmonary-renal syndrome and may be associated with detectable perinuclear antineutrophil cytoplasmic autoantibody positivity in up to a third of patients. Associated triggers may include tobacco smoking, hydrocarbon solvent exposure, and cocaine abuse. Cough, hemoptysis, and dyspnea with fatigue are the commonest presenting features. It is critical to rapidly distinguish Goodpasture's disease from other causes of pulmonary-renal syndromes such as Wegener's granulomatosis. Early and intensive treatment with plasmapheresis and immunosuppression with systemic corticosteroids pending results of diagnostic testing, and later cyclophosphamide, is often beneficial, with 90% of patients surviving the acute presentation of Goodpasture's disease. The need for hemodialysis on initial presentation, a serum creatinine >5 mg/dL, and 50% to 100% crescents on renal biopsy, portend the necessity of long-term hemodialysis. Further elucidation of the molecular pathobiology of Goodpasture's disease, particularly the regulation of involved antigen-specific T cells, may improve early diagnosis, treatment, and outcomes in this rare but potentially lethal autoimmune disorder.
KW - Alveolar hemorrhage
KW - Anti-GBM
KW - Antibodies
KW - Glomerulonephritis
KW - Goodpasture's
KW - Plasmapheresis
UR - http://www.scopus.com/inward/record.url?scp=79960402783&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960402783&partnerID=8YFLogxK
U2 - 10.1007/s12016-010-8222-2
DO - 10.1007/s12016-010-8222-2
M3 - Article
C2 - 21207195
AN - SCOPUS:79960402783
VL - 41
SP - 151
EP - 162
JO - Clinical Reviews in Allergy and Immunology
JF - Clinical Reviews in Allergy and Immunology
SN - 1080-0549
IS - 2
ER -