Aetiology
Anti-glomerular basement membrane disease is an autoimmune disease caused by antibodies to the alpha-3 chain of type IV collagen. Type IV collagen is a major structural component of all basement membranes, but the alpha-3 subtype occurs only in the basement membranes of a few tissues, principally alveoli and glomeruli.[1] No consistent trigger to disease is recognised but pulmonary haemorrhage is much more likely to occur in cigarette smokers.[7][8] Patients who smoke are more likely to present early because haemoptysis is a striking symptom likely to prompt the seeking of medical attention. The genetic backdrop is also important, with more than 90% of patients carrying HLA-DRB1*1501 or HLA-DR4.[9]
Pathophysiology
Glomerular injury is the result of autoimmunity directed against the alpha-3 chain of type IV collagen mediated by both humoral and cellular processes. Autoantibodies bound along the glomerular basement membrane are the defining feature, and many data show that they contribute to renal injury.[10][11] However, T cells are now recognised as pivotal in crescentic nephritis[12] and Th1 cells have been shown to transfer disease in the absence of any autoantibody in an animal model of anti-glomerular basement membrane (anti-GBM) disease.[13] Patients with active disease have circulating T cells specific for epitopes in the alpha-3 chain of type IV collagen restricted by the disease-associated HLA class II molecule, HLA-DR15.[14]
Smoking is common in patients presenting with pulmonary-renal syndrome and uncommon in patients presenting only with isolated renal disease. Lung damage through smoking, hydrocarbon exposure, or recent infection may play a role in unmasking the alpha-3 chain of type IV collagen present in the lung, making it available to autoimmune attack.
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