Goodpasture Syndrome
Disease Details
Family Health Simplified
- Description
- Goodpasture syndrome is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding in the lungs and kidney failure.
- Type
- Goodpasture syndrome is an autoimmune disease. It is typically not inherited in a simple Mendelian fashion; most cases are sporadic and do not follow a clear pattern of genetic transmission.
- Signs And Symptoms
- The anti–glomerular basement membrane (GBM) antibodies primarily attack the kidneys and lungs, although, generalized symptoms like malaise, weight loss, fatigue, fever, and chills are also common, as are joint aches and pains. 60–80% of those with the condition experience both lung and kidney involvement; 20–40% have kidney involvement alone, and less than 10% have lung involvement alone. Kidney symptoms usually include blood in the urine, protein in the urine, unexplained swelling of limbs or face, high amounts of urea in the blood, and high blood pressure. Lung symptoms usually antedate kidney symptoms and usually include: coughing up blood, chest pain (in less than 50% of cases overall), cough, and shortness of breath. Some other signs and symptoms that could be used to identify Goodpasture syndrome during a physical exam include an increased respiratory rate, cyanosis, crackles, hepatosplenomegaly, and hypertension.
- Prognosis
- With treatment, the five-year survival rate is >80% and fewer than 30% of affected individuals require long-term dialysis. A study performed in Australia and New Zealand demonstrated that in patients requiring renal replacement therapy (including dialysis) the median survival time is 5.93 years. Without treatment, virtually every affected person will die from either advanced kidney failure or lung hemorrhages.
- Onset
- Goodpasture syndrome can have a rapid onset, often developing over days to weeks. It commonly affects young adult males, although it can occur at any age.
- Prevalence
- The exact prevalence of Goodpasture syndrome is not well-defined but it is considered a rare disease, occurring in approximately 1 in 1 million individuals annually.
- Epidemiology
- GPS is rare, affecting about 0.5–1.8 per million people per year in Europe and Asia. It is also unusual among autoimmune diseases in that it is more common in males than in females and is also less common in blacks than whites, but more common in the Māori people of New Zealand. The peak age ranges for the onset of the disease are 20–30 and 60–70 years.
- Intractability
- Goodpasture syndrome is considered a serious and potentially life-threatening condition, but it is not necessarily intractable. Early diagnosis and prompt treatment can significantly improve the outcome. Treatment typically includes immunosuppressive medications, plasmapheresis (to remove antibodies from the blood), and sometimes dialysis if kidney function is severely affected. However, the success of treatment can vary and long-term management may be required.
- Disease Severity
- Goodpasture syndrome is considered a severe disease. It can lead to life-threatening kidney failure and lung hemorrhage if not treated promptly. This autoimmune disorder requires immediate medical intervention to manage symptoms and prevent rapid progression.
- Healthcare Professionals
- Disease Ontology ID - DOID:9808
- Pathophysiology
- GPS is caused by abnormal plasma cell production of anti-GBM antibodies. The major target of these abnormal antibodies is the non-collagen domain of the alpha-3 chain of type 4 collagen, which is mostly found in the basal membranes of glomerular and alveolar capillaries, explaining the obscurely specific symptoms of this condition. This preferred targeting of these alpha-3 collagen chains specifically in the basal membranes of glomerular and alveolar capillaries can be explained by the higher accessible exposure of epitopes, a larger expansion of the alpha-3 collagen units, and because these alpha-3 collagen chains structurally provide higher accessibility for the targeting antibodies. These antibodies bind their reactive epitopes to the basement membranes and activate the complement cascade, leading to the death of tagged cells. A specific antibody and epitope binding that shows the highest affinity and is pathogenic occurs between GPA antibodies and the anti-GBM epitope region, designated EA, which is residues 17-31 of the alpha 3 subunit of non-collagenous domain of type IV collagen. T cells are also implicated, though it is generally considered a type II hypersensitivity reaction.
- Carrier Status
- Goodpasture syndrome is not typically associated with a carrier status. It is an autoimmune disease characterized by the presence of autoantibodies against the glomerular basement membrane in the kidneys and the alveolar basement membrane in the lungs. These autoantibodies lead to rapid glomerulonephritis and pulmonary hemorrhage. It is not inherited in a manner that would involve carriers, as it usually occurs sporadically.
- Mechanism
-
Goodpasture syndrome, also known as anti-glomerular basement membrane (anti-GBM) disease, is an autoimmune condition characterized by the presence of autoantibodies against the basement membranes in the kidneys and lungs.
**Mechanism:**
1. **Autoantibody Formation:** The immune system generates antibodies targeting the alpha-3 chain of type IV collagen, a crucial component of the basement membrane in the glomeruli of the kidneys and alveoli of the lungs.
2. **Binding and Damage:** These autoantibodies bind to the basement membrane, specifically in the glomeruli and alveoli.
3. **Immune Activation:** The binding of antibodies activates the complement system and recruits inflammatory cells such as neutrophils and macrophages.
4. **Tissue Injury:** The ensuing immune response leads to inflammation and damage in the glomeruli (glomerulonephritis) and alveoli (alveolar hemorrhage), resulting in kidney failure and lung hemorrhage.
**Molecular Mechanisms:**
1. **Antigenic Target:** The primary target is the non-collagenous (NC1) domain of the alpha-3 chain of type IV collagen (COL4A3).
2. **Gene Involvement:** Genetic predispositions may play a role, particularly polymorphisms in the COL4A3 and COL4A4 genes, although environmental triggers are also implicated.
3. **Antibody Interaction:** Anti-GBM antibodies specifically bind conformational epitopes in the NC1 domain, initiating the immune response.
4. **Complement Activation:** The classical complement pathway is activated following antibody binding, leading to the formation of the membrane attack complex and tissue injury.
5. **Inflammatory Cascade:** A local inflammatory response is amplified by cytokines like TNF-alpha and IL-1, further recruiting immune cells and perpetuating the damage.
Understanding these mechanisms highlights the complex interplay between genetic factors and immune responses in Goodpasture syndrome and underscores the need for targeted treatments to mitigate these processes. - Treatment
- The major mainstay of treatment for GPS is plasmapheresis, a procedure in which the affected person's blood is sent through a centrifuge and the various components separated based on weight. The plasma contains the anti-GBM antibodies that attack the affected person's lungs and kidneys, and is filtered out. The other parts of the blood (the red blood cells, white blood cells, and platelets) are recycled and intravenously reinfused. Most individuals affected by the disease also need to be treated with immunosuppressant drugs, especially cyclophosphamide, prednisone, and rituximab, to prevent the formation of new anti-GBM antibodies so as to prevent further damage to the kidneys and lungs. Other, less toxic immunosuppressants such as azathioprine may be used to maintain remission.
- Compassionate Use Treatment
-
Goodpasture syndrome, also known as anti-glomerular basement membrane (anti-GBM) disease, is typically treated with corticosteroids and immunosuppressive medications such as cyclophosphamide, along with plasmapheresis to remove circulating antibodies. While these are the standard treatments, there are also compassionate use and off-label treatments being explored:
1. **Rituximab**: Primarily used for other autoimmune disorders and certain cancers, rituximab has been used off-label in Goodpasture syndrome to target B cells that produce pathogenic antibodies.
2. **Eculizumab**: Though mainly used in conditions like paroxysmal nocturnal hemoglobinuria, eculizumab has been investigated for its role in Goodpasture syndrome because it inhibits the complement system, which is part of the disease's pathogenic mechanism.
3. **Mycophenolate mofetil**: Known for its use in organ transplantation to prevent rejection, this drug has been considered as an experimental adjunct therapy in Goodpasture syndrome for its immunosuppressive properties.
4. **Belimumab**: Used in systemic lupus erythematosus, belimumab is being studied for its potential to block B-cell activating factor, thus potentially reducing antibody production in Goodpasture syndrome.
Please note that the use of these treatments should be closely monitored by healthcare professionals, given the complexity and potential risks involved. - Lifestyle Recommendations
-
Lifestyle recommendations for Goodpasture Syndrome primarily focus on managing symptoms and supporting overall health. Here are some important guidelines:
1. **Medication Adherence**: Follow your prescribed treatment plan, including medications such as immunosuppressants and corticosteroids.
2. **Avoid Smoking**: Refrain from smoking as it can worsen lung damage.
3. **Healthy Diet**: Eat a balanced diet rich in fruits, vegetables, lean proteins, and whole grains to support your immune system.
4. **Hydration**: Drink plenty of fluids unless advised otherwise by your doctor due to kidney complications.
5. **Rest and Recovery**: Ensure adequate rest to help your body recover, especially during flare-ups.
6. **Avoid Infections**: Minimize exposure to infections by practicing good hygiene and avoiding crowded places during flu seasons.
7. **Regular Checkups**: Schedule and attend regular follow-up appointments with your healthcare provider to monitor kidney and lung function.
8. **Manage Stress**: Incorporate stress-reducing activities like yoga, meditation, or gentle exercise into your routine.
Always consult your healthcare provider for personalized advice. - Medication
-
Goodpasture syndrome is treated primarily with medications aimed at reducing the immune response and managing symptoms. The standard treatment regimen includes:
1. **Corticosteroids:** Prednisone is commonly used to reduce inflammation and suppress the immune system.
2. **Immunosuppressive drugs:** Cyclophosphamide or azathioprine can help reduce the activity of the immune system.
3. **Plasmapheresis:** This procedure removes antibodies from the blood that are attacking the kidneys and lungs.
These treatments are often used in combination to effectively manage the condition. Regular monitoring and adjustments based on response to therapy and side effects are essential. - Repurposable Drugs
-
Current repurposable drugs under investigation for Goodpasture syndrome include:
1. **Rituximab**: Originally used for certain types of cancer and autoimmune diseases, it targets B cells and can help reduce the immune response against the kidneys and lungs.
2. **Mycophenolate mofetil (MMF)**: Commonly used in organ transplantation, MMF suppresses the immune response and may help in reducing autoantibody production in Goodpasture syndrome.
Please consult a medical professional for specific treatment advice. - Metabolites
- Goodpasture syndrome is an autoimmune disease affecting the kidneys and lungs. Specific metabolite profiles associated with Goodpasture syndrome are not well-characterized in scientific literature. However, common laboratory findings may include elevated levels of serum creatinine and blood urea nitrogen (BUN) due to kidney impairment. Additionally, anti-glomerular basement membrane (anti-GBM) antibodies are a key marker for diagnosis. Detailed metabolic profiling would require specialized studies.
- Nutraceuticals
- Goodpasture syndrome is an autoimmune disease affecting the kidneys and lungs. Nutraceuticals are not typically a part of standard treatment for Goodpasture syndrome. The primary treatment involves immunosuppressive medications like corticosteroids and cyclophosphamide, as well as plasmapheresis to remove antibodies from the bloodstream. Nanotechnology-based treatments are still in the research phase and not part of current clinical practice for this condition. Nutritional supplements should only be considered under a healthcare provider's guidance.
- Peptides
- Goodpasture syndrome, also known as anti-glomerular basement membrane (anti-GBM) disease, involves the immune system creating antibodies against the basement membrane in kidneys and lungs. This autoimmune response leads to damage in these organs. Peptides are not a direct treatment for Goodpasture syndrome. Instead, management typically involves immunosuppressive therapy and plasmapheresis to remove the harmful antibodies. "Nan" does not appear relevant to the context of Goodpasture syndrome. If you meant "NAN" as an abbreviation for something specific, please clarify.