Goodpasture syndrome , also known as anti-glomerular basement membrane disease, is a rareautoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and kidney failure. It is thought to attack the alpha-3 subunit of type IV collagen, which has therefore been referred to as Goodpasture's antigen. Goodpasture syndrome may quickly result in permanent lung and kidney damage, often leading to death. It is treated with medications that suppress the immune system such as corticosteroids and cyclophosphamide, and with plasmapheresis, in which the antibodies are removed from the blood. The disease was first described by an American pathologist Ernest Goodpasture of Vanderbilt University in 1919 and was later named in his honor.
Its precise cause is unknown, but an insult to the blood vessels taking blood from and to the lungs is believed to be required to allow the anti-GBM antibodies to come into contact with the alveoli. Examples of such an insult include: exposure to organic solvents or hydrocarbons, exposure to tobacco smoke, certain alleles, infection, cocaine inhalation, metal dust inhalation, bacteraemia, sepsis, high-oxygen environments, and treatment with antilymphocytic treatment.
Pathophysiology
GPS is caused by abnormal plasma cell production of anti-GBM antibodies. The anti-GBM antibodies attack the alveoli and glomerulibasement membranes. These antibodies bind their reactive epitopes to the basement membranes and activate the complement cascade, leading to the death of tagged cells. T cells are also implicated, though it is generally considered a type II hypersensitivity reaction.
Diagnosis
The diagnosis of GPS is often difficult, as numerous other diseases can cause the various manifestations of the condition and the condition itself is rare. The most accurate means of achieving the diagnosis is testing the affected tissues by means of a biopsy, especially the kidney, as it is the best-studied organ for obtaining a sample for the presence of anti-GBM antibodies. On top of the anti-GBM antibodies implicated in the disease, about one in three of those affected also has cytoplasmic antineutrophilic antibodies in their bloodstream, which often predates the anti-GBM antibodies by about a few months or even years. The later the disease is diagnosed, the worse the outcome is for the affected person.
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 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.
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 the median survival time is 5.93 years. Without treatment, virtually every affected person will die from either advanced kidney failure or lung hemorrhages.
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.
