Native - Bovine Kidney
Uniprot ID: Q28084
mRNA RefSeq: Not currently available
Protein RefSeq: Not currently available
Autoantibodies to glomerular basement membrane (GBM) are known to mediate the rapidly progressive glomerulonephritis (with or without pulmonary haemorrhage) typical of Goodpasture syndrome. Assay of anti-GBM antibodies is valuable in three clinical conditions: a) patients with acute renal failure where post- and pre-renal causes seem unlikely; b) patients with increasing serum creatinine levels together with haematuria and casts, and c) patients with pulmonary haemorrhage. Early detection of anti-GBM antibodies in such conditions followed by immediate immunotherapy may greatly improve the disease prognosis.
Patients with Goodpasture syndrome can exhibit clinical features typical of autoimmune vasculitic conditions. It has therefore been recommended that anti-GBM antibodies be assayed together with anti-neutrophil cytoplasmic antibodies (ANCA) in pulmonary renal syndromes.
Anti-GBM antibodies distribute along the GBM in a linear fashion as seen by direct immunofluorescence microscopy, indicative of reactivity with a specific GBM antigen that has been identified as the NC1 domain of α3 type IV collagen. Collagen IV interweaves with laminins, nidogen and sulphated proteoglycans to assemble basement membranes. In glomerular basement membrane three distinct α chains (α3.α4.α5) of type IV collagen assemble as a triple helical protomer with their respective C-terminal non-collagenous domains (NC1) forming a trimer at one extreme.
Two NC1 trimers unite to form a hexamer; these hexamers create collagenous networks by uniting four triple helical 7S domains at the N-terminal. Super-coiling and disulphide bridges further stabilise the network. Two dominant epitopes have been identified on α3(IV) NC1, both of which are cryptic in nature and inaccessible for autoantibody binding unless dissociation of the NC1 hexamer occurs. The epitopes appear to be conformation-dependent and are destroyed by reduction of disulphide bridges.
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Collagen type IV NC1 domain