Antiglomerular Basement Membrane Disease

Patients who develop autoantibodies directed against glomerular basement antigens frequently develop a glomerulonephritis termed antiglomerular basement membrane (anti-GBM) disease. When they present with lung hemorrhage and glomerulonephritis, they have a pulmonary-renal syndrome called Goodpasture's syndrome.

 The target epitopes for this autoimmune disease lie in the quaternary structure of alpha 3 NC1 domain of collagen IV.

 MHC-restricted T cells initiate the autoantibody response because humans are not tolerant to the epitopes created by this quaternary structure. The epitopes are normally sequestered in the collagen IV hexamer and can be exposed by infection, smoking, oxidants, or solvents.

 Goodpasture's syndrome appears in two age groups: in young men in their late 20s and in men and women in their 60–70s. Disease in the younger age group is usually explosive, with hemoptysis, a sudden fall in hemoglobin, fever, dyspnea, and hematuria. Hemoptysis is largely confined to smokers, and those who present with lung hemorrhage as a group do better than older populations who have prolonged, asymptomatic renal injury; presentation with oliguria is often associated with a particularly bad outcome.

The performance of an urgent kidney biopsy is important in suspected cases of Goodpasture's syndrome to confirm the diagnosis and assess prognosis. Renal biopsies typically show focal or segmental necrosis that later, with aggressive destruction of the capillaries by cellular proliferation, leads to crescent formation in Bowman's space . As these lesions progress, there is concomitant interstitial nephritis with fibrosis and tubular atrophy.

The presence of anti-GBM antibodies and complement is recognized on biopsy by linear immunofluorescent staining for IgG (rarely IgA). In testing serum for anti-GBM antibodies, it is particularly important that the alpha-3 NC1 domain of collagen IV alone be used as the target. This is because nonnephritic antibodies against the alpha-1 NC1 domain are seen in paraneoplastic syndromes and cannot be discerned from assays that use whole basement membrane fragments as the binding target. Between 10–15% of sera from patients with Goodpasture's syndrome also contain ANCA antibodies against myeloperoxidase. This subset of patients has a vasculitis-associated variant, which has a surprisingly good prognosis with treatment.

 Prognosis at presentation is worse if there are
* >50% crescents on renal biopsy with advanced fibrosis
* serum creatinine is >5–6 mg/dL
* oliguria is present
* there is a need for acute dialysis.

 Although frequently attempted, most of these latter patients will not respond to plasmapheresis and steroids. Patients with advanced renal failure who present with hemoptysis should still be treated for their lung hemorrhage, as it responds to plasmapheresis and can be lifesaving. Treated patients with less severe disease typically respond to 8–10 treatments of plasmapheresis accompanied by oral prednisone and cyclophosphamide in the first 2 weeks. Kidney transplantation is possible, but because there is risk of recurrence, experience suggests that patients should wait for 6 months and until serum antibodies are undetectable.