Background Basement Membrane and Type IV Collagen

Major histocompatibility complex (MHC) Class 11 molecules are believed to bind to a 3 (IV) NCI epitopes stimulating T-cell recognition and modulating the humoral response. Using a mouse model of GBM disease, Kalluri and colleagues (30) showed that all mice strains immunized with a3 (IV) NCI peptides developed anti a3 (IV) NCI antibodies but the development of pulmonary and renal disease was restricted to Swiss James Lambert (SJL) mice that possessed MHC H-2 . B6 (H-2 ), BALB/c (H-2 ), DBA/2 (H-2 ) mice developed only renal disease and A/J (H-2 ), AKR (H-2 ), and CBA (H-2 ) mice showed no evidence of either renal or pulmonary disease. In addition, these investigators showed that passive transfer of isogenic a3 (IV) NCI antibodies into T-cell receptor-deficient mice did not cause renal or pulmonary injury. Further immunohistochemical studies supported a Thl response pattern with increased presence of interleukin (IL)-12, lL-4, IL-10, and 

An intact Th-l type immune response is required for the development of experimental anti-GBMA disease (32). IL-12 is required for the Th 1 response and mice lacking lL-12 do not develop raial disease in a model of antibody-induced glomerulonephritis (33). In contrast, mice that are genetically deficient of IFN-y —I— have increased renal damage in this model suggesting a protective effect for IFN-y. 

The most common sign is pallor, which is present in up to 90% of cases (23,58). Between one-third and half of patients have crackles or rhonchi present on chest auscultation (58). Lower extremity edema occurs in 25% to 32% of patients (23,58). Other physical examination findings include tachycardia, tachypnea, and hepatosplenomegaly. Ophthalmic findings occur infrequently and include retinal hemorrhage and detachment with IgG deposition in Burch s membrane and the basement membranes of the choroidal vessels (63,64). 

Although the clinical manifestations of Goodpasture s syndrome are usually limited to the lungs and kidneys, cerebral vasculitis occasionally associated with seizures has been described (66-68). Other autoimmune disorders that have been associated with anti-GBMAs include myasthenia gravis (69), primary bihary cirrhosis (70), polyartaltis nodosa (71), cardiac disease (72), and epidermolysis buUosa acquisita (72). 

An incorrect diagnosis of Goodpasture s syndrome was made in an individual with lung adenocarcinoma and hemoptysis who had an elevated anti-GBMA performed in a commercial reference laboratory (80). Subsequent evaluation demonstrated that the antibodies were directed against al(IV) rather than ot3(IV) collagen. Anti-GBMAs may also be detected in individuals with human immunodeficiency virus (HIV) infection and no clinical renal or pulmonary disease (81,82). 

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