Anti-glomerular basement membrane disease is a rare condition in which the body produces antibodies that attack the basement membrane of blood vessels, specifically in the kidneys (glomerulonephritis) and lungs (pulmonary hemorrhage) is classified as an immune-complex small vessel vasculitis.
Goodpasture syndrome, named after Ernest Goodpasture, who first described it in 1919, is a rare autoimmune disorder that affects both the lungs and kidneys. While Goodpasture syndrome is often used interchangeably with anti-glomerular basement membrane disease, it refers explicitly to renal and pulmonary involvement cases. The disease may also present differently as glomerulonephritis alone.
Epidemiology
Anti-GBM disease accounts for only 5% of all cases of glomerulonephritis and 10-20% of rapidly progressive crescentic glomerulonephritis in the United States. Internationally, the disease is seen in 10-20% of rapidly progressive glomerulonephritis cases. It is more common among whites and has a bimodal distribution with respect to age and sex. The first peak occurs in men in their second and third decades of life, while the second peak occurs in women in their sixth and seventh decades of life.
Anti-GBM disease has been found to be triggered by treatment with alemtuzumab, an anti-CD52 monoclonal antibody that is commonly used to treat relapsing multiple sclerosis. It is believed that this increased incidence may be due to the loss of specific regulatory T cell subsets or abnormal repopulation of immune cells after depletion caused by alemtuzumab.
Anatomy
Pathophysiology
Anti-GBM antibodies are immune responses targeting a specific epitope located on the alpha-3 chain of type IV collagen. This chain is found only in specialized basement membranes, such as those in the kidneys and lungs. When these antibodies bind to the antigen in these organs, they trigger an inflammatory response that leads to tissue destruction, resulting in rapid pulmonary hemorrhage and proliferative glomerulonephritis.
The exact cause of the formation of these antibodies is not fully understood. However, it is believed that an environmental factor, such as exposure to hydrocarbons or smoking, is necessary to unmask the antigen to the immune system. The mechanism of tissue damage caused by anti-GBM antibodies involves the activation of the complement system. This leads to the recruitment of proinflammatory cells and the release of proteolytic enzymes and proinflammatory cytokines, chemokines.
This results in damage to the endothelial cells, detachment of the cells from the underlying basement membrane, and accumulation of fibrin. This ultimately leads to breaks in the basement membrane, leakage of plasma proteins and cells into the Bowman space, and the development of crescents. Approximately 20-40% of patients with anti-GBM antibodies also have antineutrophilic cytoplasmic antibodies (ANCAs), most commonly myeloperoxidase (MPO-ANCAs).
It is thought that renal involvement in ANCA vasculitis, a disease that affects the blood vessels, leads to the exposure of basement membrane antigens and the formation of anti-GBM antibodies in these patients. This suggests that ANCA vasculitis may play a role in developing anti-GBM antibodies, specifically by exposing basement membrane antigens in the kidneys. This connection between ANCA vasculitis and anti-GBM antibodies highlights the complex interplay between the body’s immune system and various organ systems.
Etiology
Anti-GBM disease is caused by autoantibodies that target the NC1 domain of the alpha-3 chain of type IV collagen, and both genetic and environmental factors contribute to its development. Studies have shown a strong association with HLA-DR2, specifically HLA-DRB1 alleles (1501 and 1502), HLA-DQA1 01, and HLA-DQB1 06.
HLA-DRB1*1501 and 1502 alleles also increase susceptibility to the disease, while HLA-DR1 and HLA-DR7 offer protection. Environmental factors linked to the disease include smoking and exposure to hydrocarbons or respiratory pathogens. Recently, there has been reports of COVID-19 being associated with new and recurrent cases of anti-GBM disease.
Genetics
Prognostic Factors
Anti-GBM disease, also known as Goodpasture’s Syndrome, is a severe and rapidly progressing illness. Historically, this disease’s mortality rate was as high as 90-95%. However, with the introduction of treatments such as immunosuppression and plasmapheresis, the prognosis for patients has improved significantly.
Currently, the patient survival rate is around 85%, while the rate of renal survival is around 60%. It is important to note that the outlook for patients with Anti-GBM disease can vary depending on the severity of their condition at the time of diagnosis.
Clinical History
Clinical History
Anti-GBM disease can affect the kidneys and the lungs, with pulmonary hemorrhage as a severe complication. The symptoms of the disease can develop gradually or suddenly, including flulike illness, joint pain, anemia, pallor, weakness, dyspnea, dry cough, fever, massive hemoptysis, acute respiratory failure, asphyxia, and death.
Additionally, patients may present with abrupt onset of oliguria or anuria and may pass tea-colored urine as a result of hematuria. In some cases, the renal involvement may be more insidious, with the patient remaining asymptomatic initially and the glomerulonephritis progressing slowly until the development of uremic symptoms.
Physical Examination
Physical Examination
In Anti-GBM disease, physical examination may reveal signs of kidney involvement, such as swelling of the face, hands, or feet and blood in the urine. Signs of lung involvement include crackles or decreased breath sounds and signs of severe respiratory distress, such as rapid heart rate and a bluish discoloration of the skin and mucous membranes. Additionally, the patient may appear pale due to anemia.
In severe cases, the patient’s condition may be critical, and they may be experiencing hemorrhagic shock, which is a severe decrease in blood flow that can lead to tissue damage and organ failure. They may also be experiencing respiratory failure. In these situations, immediate medical intervention is typically required, such as providing volume resuscitation to increase blood flow and using a ventilator to support the patient’s breathing. During a chest examination, crackles (rales) are heard.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Differential Diagnoses
Acute Kidney Injury
Churg-Strauss Syndrome
Crescentic Glomerulonephritis
Microscopic Polyangiitis
Rapidly Progressive Glomerulonephritis
Thrombotic Thrombocytopenia Purpura
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Anti-GBM nephritis is a rapidly progressive disease that can be fatal if not treated promptly. The patient should be transferred to a tertiary care centre for diagnosis and treatment, which usually includes plasmapheresis in combination with corticosteroids and immunosuppressant medication like cyclophosphamide or azathioprine.
Other options include immunoadsorption or cyclosporine. Patients with severe pulmonary hemorrhage may require intubation, and ventilation support. Additionally, patients may present with hemorrhagic shock and require blood transfusion and hemodynamic monitoring. Patients with advanced kidney failure may need dialysis. While in the hospital, patients should receive supportive care such as adequate nutrition, prophylaxis for deep vein thrombosis and stress ulcers, and good blood pressure control.
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Anti-glomerular basement membrane disease is a rare condition in which the body produces antibodies that attack the basement membrane of blood vessels, specifically in the kidneys (glomerulonephritis) and lungs (pulmonary hemorrhage) is classified as an immune-complex small vessel vasculitis.
Goodpasture syndrome, named after Ernest Goodpasture, who first described it in 1919, is a rare autoimmune disorder that affects both the lungs and kidneys. While Goodpasture syndrome is often used interchangeably with anti-glomerular basement membrane disease, it refers explicitly to renal and pulmonary involvement cases. The disease may also present differently as glomerulonephritis alone.
Anti-GBM disease accounts for only 5% of all cases of glomerulonephritis and 10-20% of rapidly progressive crescentic glomerulonephritis in the United States. Internationally, the disease is seen in 10-20% of rapidly progressive glomerulonephritis cases. It is more common among whites and has a bimodal distribution with respect to age and sex. The first peak occurs in men in their second and third decades of life, while the second peak occurs in women in their sixth and seventh decades of life.
Anti-GBM disease has been found to be triggered by treatment with alemtuzumab, an anti-CD52 monoclonal antibody that is commonly used to treat relapsing multiple sclerosis. It is believed that this increased incidence may be due to the loss of specific regulatory T cell subsets or abnormal repopulation of immune cells after depletion caused by alemtuzumab.
Anti-GBM antibodies are immune responses targeting a specific epitope located on the alpha-3 chain of type IV collagen. This chain is found only in specialized basement membranes, such as those in the kidneys and lungs. When these antibodies bind to the antigen in these organs, they trigger an inflammatory response that leads to tissue destruction, resulting in rapid pulmonary hemorrhage and proliferative glomerulonephritis.
The exact cause of the formation of these antibodies is not fully understood. However, it is believed that an environmental factor, such as exposure to hydrocarbons or smoking, is necessary to unmask the antigen to the immune system. The mechanism of tissue damage caused by anti-GBM antibodies involves the activation of the complement system. This leads to the recruitment of proinflammatory cells and the release of proteolytic enzymes and proinflammatory cytokines, chemokines.
This results in damage to the endothelial cells, detachment of the cells from the underlying basement membrane, and accumulation of fibrin. This ultimately leads to breaks in the basement membrane, leakage of plasma proteins and cells into the Bowman space, and the development of crescents. Approximately 20-40% of patients with anti-GBM antibodies also have antineutrophilic cytoplasmic antibodies (ANCAs), most commonly myeloperoxidase (MPO-ANCAs).
It is thought that renal involvement in ANCA vasculitis, a disease that affects the blood vessels, leads to the exposure of basement membrane antigens and the formation of anti-GBM antibodies in these patients. This suggests that ANCA vasculitis may play a role in developing anti-GBM antibodies, specifically by exposing basement membrane antigens in the kidneys. This connection between ANCA vasculitis and anti-GBM antibodies highlights the complex interplay between the body’s immune system and various organ systems.
Anti-GBM disease is caused by autoantibodies that target the NC1 domain of the alpha-3 chain of type IV collagen, and both genetic and environmental factors contribute to its development. Studies have shown a strong association with HLA-DR2, specifically HLA-DRB1 alleles (1501 and 1502), HLA-DQA1 01, and HLA-DQB1 06.
HLA-DRB1*1501 and 1502 alleles also increase susceptibility to the disease, while HLA-DR1 and HLA-DR7 offer protection. Environmental factors linked to the disease include smoking and exposure to hydrocarbons or respiratory pathogens. Recently, there has been reports of COVID-19 being associated with new and recurrent cases of anti-GBM disease.
Anti-GBM disease, also known as Goodpasture’s Syndrome, is a severe and rapidly progressing illness. Historically, this disease’s mortality rate was as high as 90-95%. However, with the introduction of treatments such as immunosuppression and plasmapheresis, the prognosis for patients has improved significantly.
Currently, the patient survival rate is around 85%, while the rate of renal survival is around 60%. It is important to note that the outlook for patients with Anti-GBM disease can vary depending on the severity of their condition at the time of diagnosis.
Clinical History
Anti-GBM disease can affect the kidneys and the lungs, with pulmonary hemorrhage as a severe complication. The symptoms of the disease can develop gradually or suddenly, including flulike illness, joint pain, anemia, pallor, weakness, dyspnea, dry cough, fever, massive hemoptysis, acute respiratory failure, asphyxia, and death.
Additionally, patients may present with abrupt onset of oliguria or anuria and may pass tea-colored urine as a result of hematuria. In some cases, the renal involvement may be more insidious, with the patient remaining asymptomatic initially and the glomerulonephritis progressing slowly until the development of uremic symptoms.
Physical Examination
In Anti-GBM disease, physical examination may reveal signs of kidney involvement, such as swelling of the face, hands, or feet and blood in the urine. Signs of lung involvement include crackles or decreased breath sounds and signs of severe respiratory distress, such as rapid heart rate and a bluish discoloration of the skin and mucous membranes. Additionally, the patient may appear pale due to anemia.
In severe cases, the patient’s condition may be critical, and they may be experiencing hemorrhagic shock, which is a severe decrease in blood flow that can lead to tissue damage and organ failure. They may also be experiencing respiratory failure. In these situations, immediate medical intervention is typically required, such as providing volume resuscitation to increase blood flow and using a ventilator to support the patient’s breathing. During a chest examination, crackles (rales) are heard.
Differential Diagnoses
Acute Kidney Injury
Churg-Strauss Syndrome
Crescentic Glomerulonephritis
Microscopic Polyangiitis
Rapidly Progressive Glomerulonephritis
Thrombotic Thrombocytopenia Purpura
Anti-GBM nephritis is a rapidly progressive disease that can be fatal if not treated promptly. The patient should be transferred to a tertiary care centre for diagnosis and treatment, which usually includes plasmapheresis in combination with corticosteroids and immunosuppressant medication like cyclophosphamide or azathioprine.
Other options include immunoadsorption or cyclosporine. Patients with severe pulmonary hemorrhage may require intubation, and ventilation support. Additionally, patients may present with hemorrhagic shock and require blood transfusion and hemodynamic monitoring. Patients with advanced kidney failure may need dialysis. While in the hospital, patients should receive supportive care such as adequate nutrition, prophylaxis for deep vein thrombosis and stress ulcers, and good blood pressure control.
medtigo
Antiglomerular Basement Membrane Disease
Updated :
August 30, 2023
Anti-glomerular basement membrane disease is a rare condition in which the body produces antibodies that attack the basement membrane of blood vessels, specifically in the kidneys (glomerulonephritis) and lungs (pulmonary hemorrhage) is classified as an immune-complex small vessel vasculitis.
Goodpasture syndrome, named after Ernest Goodpasture, who first described it in 1919, is a rare autoimmune disorder that affects both the lungs and kidneys. While Goodpasture syndrome is often used interchangeably with anti-glomerular basement membrane disease, it refers explicitly to renal and pulmonary involvement cases. The disease may also present differently as glomerulonephritis alone.
Anti-GBM disease accounts for only 5% of all cases of glomerulonephritis and 10-20% of rapidly progressive crescentic glomerulonephritis in the United States. Internationally, the disease is seen in 10-20% of rapidly progressive glomerulonephritis cases. It is more common among whites and has a bimodal distribution with respect to age and sex. The first peak occurs in men in their second and third decades of life, while the second peak occurs in women in their sixth and seventh decades of life.
Anti-GBM disease has been found to be triggered by treatment with alemtuzumab, an anti-CD52 monoclonal antibody that is commonly used to treat relapsing multiple sclerosis. It is believed that this increased incidence may be due to the loss of specific regulatory T cell subsets or abnormal repopulation of immune cells after depletion caused by alemtuzumab.
Anti-GBM antibodies are immune responses targeting a specific epitope located on the alpha-3 chain of type IV collagen. This chain is found only in specialized basement membranes, such as those in the kidneys and lungs. When these antibodies bind to the antigen in these organs, they trigger an inflammatory response that leads to tissue destruction, resulting in rapid pulmonary hemorrhage and proliferative glomerulonephritis.
The exact cause of the formation of these antibodies is not fully understood. However, it is believed that an environmental factor, such as exposure to hydrocarbons or smoking, is necessary to unmask the antigen to the immune system. The mechanism of tissue damage caused by anti-GBM antibodies involves the activation of the complement system. This leads to the recruitment of proinflammatory cells and the release of proteolytic enzymes and proinflammatory cytokines, chemokines.
This results in damage to the endothelial cells, detachment of the cells from the underlying basement membrane, and accumulation of fibrin. This ultimately leads to breaks in the basement membrane, leakage of plasma proteins and cells into the Bowman space, and the development of crescents. Approximately 20-40% of patients with anti-GBM antibodies also have antineutrophilic cytoplasmic antibodies (ANCAs), most commonly myeloperoxidase (MPO-ANCAs).
It is thought that renal involvement in ANCA vasculitis, a disease that affects the blood vessels, leads to the exposure of basement membrane antigens and the formation of anti-GBM antibodies in these patients. This suggests that ANCA vasculitis may play a role in developing anti-GBM antibodies, specifically by exposing basement membrane antigens in the kidneys. This connection between ANCA vasculitis and anti-GBM antibodies highlights the complex interplay between the body’s immune system and various organ systems.
Anti-GBM disease is caused by autoantibodies that target the NC1 domain of the alpha-3 chain of type IV collagen, and both genetic and environmental factors contribute to its development. Studies have shown a strong association with HLA-DR2, specifically HLA-DRB1 alleles (1501 and 1502), HLA-DQA1 01, and HLA-DQB1 06.
HLA-DRB1*1501 and 1502 alleles also increase susceptibility to the disease, while HLA-DR1 and HLA-DR7 offer protection. Environmental factors linked to the disease include smoking and exposure to hydrocarbons or respiratory pathogens. Recently, there has been reports of COVID-19 being associated with new and recurrent cases of anti-GBM disease.
Anti-GBM disease, also known as Goodpasture’s Syndrome, is a severe and rapidly progressing illness. Historically, this disease’s mortality rate was as high as 90-95%. However, with the introduction of treatments such as immunosuppression and plasmapheresis, the prognosis for patients has improved significantly.
Currently, the patient survival rate is around 85%, while the rate of renal survival is around 60%. It is important to note that the outlook for patients with Anti-GBM disease can vary depending on the severity of their condition at the time of diagnosis.
Clinical History
Anti-GBM disease can affect the kidneys and the lungs, with pulmonary hemorrhage as a severe complication. The symptoms of the disease can develop gradually or suddenly, including flulike illness, joint pain, anemia, pallor, weakness, dyspnea, dry cough, fever, massive hemoptysis, acute respiratory failure, asphyxia, and death.
Additionally, patients may present with abrupt onset of oliguria or anuria and may pass tea-colored urine as a result of hematuria. In some cases, the renal involvement may be more insidious, with the patient remaining asymptomatic initially and the glomerulonephritis progressing slowly until the development of uremic symptoms.
Physical Examination
In Anti-GBM disease, physical examination may reveal signs of kidney involvement, such as swelling of the face, hands, or feet and blood in the urine. Signs of lung involvement include crackles or decreased breath sounds and signs of severe respiratory distress, such as rapid heart rate and a bluish discoloration of the skin and mucous membranes. Additionally, the patient may appear pale due to anemia.
In severe cases, the patient’s condition may be critical, and they may be experiencing hemorrhagic shock, which is a severe decrease in blood flow that can lead to tissue damage and organ failure. They may also be experiencing respiratory failure. In these situations, immediate medical intervention is typically required, such as providing volume resuscitation to increase blood flow and using a ventilator to support the patient’s breathing. During a chest examination, crackles (rales) are heard.
Differential Diagnoses
Acute Kidney Injury
Churg-Strauss Syndrome
Crescentic Glomerulonephritis
Microscopic Polyangiitis
Rapidly Progressive Glomerulonephritis
Thrombotic Thrombocytopenia Purpura
Anti-GBM nephritis is a rapidly progressive disease that can be fatal if not treated promptly. The patient should be transferred to a tertiary care centre for diagnosis and treatment, which usually includes plasmapheresis in combination with corticosteroids and immunosuppressant medication like cyclophosphamide or azathioprine.
Other options include immunoadsorption or cyclosporine. Patients with severe pulmonary hemorrhage may require intubation, and ventilation support. Additionally, patients may present with hemorrhagic shock and require blood transfusion and hemodynamic monitoring. Patients with advanced kidney failure may need dialysis. While in the hospital, patients should receive supportive care such as adequate nutrition, prophylaxis for deep vein thrombosis and stress ulcers, and good blood pressure control.
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