Renal distribution of collagen type IV α chains in autosomal-dominant Alport syndrome

Background Autosomal-dominant Alport syndrome is a recognized, but relatively uncommon, form of Alport syndrome. Recently, mutations in theCOL4A3 andCOL4A4 genes, which encode collagen type IV α3 and α4 chains, respectively, have been shown to cause the disease. However, the distribution of α(IV) chains has yet to be determined. Methods To clarify the renal distribution of α(IV) chains, immunohistochemistry of α1(IV) to α6(IV) chains was performed, using chain-specific monoclonal antibodies, raised by us, and an antigen retrieval procedure. Paraffin-embedded renal sections, obtained from 8 patients from 3 families with the disease, were examined. Results The distribution of all 6 α(IV) chains was not significantly different between the 8 patients and the controls. Collagen type IV α1 and α2 chains were ubiquitously expressed, while α3 to α6 chains were detected in the basement membranes of the glomerulus and Bowman's capsule, and/or part of the tubular basement membranes. Conclusions Our findings contrast with those of X-linked and autosomal-recessive Alport syndrome. The distribution pattern of α(IV) chains may provide a useful means of distinguishing the different forms of Alport syndrome.