Epidermal basement membrane α5(IV) expression in females with Alport syndrome and severity of renal disease

Abstract

Background. X-linked Alport syndrome is a progressive nephritis caused by mutations of the COL4A5 gene. This gene encodes the collagen α5(IV) chain, which is abnormally distributed in the glomerular basement membrane (GBM) and epidermal basement membrane (EBM). It has been reported a negative correlation between α5(IV) chain distribution in EBM and the degree of proteinuria in heterozygous females with Alport syndrome. Methods. In the present study, we evaluated the distribution of the α5(IV) chain in the EBM and the degree of proteinuria in 22 females with X-linked Alport syndrome. The distribution of the cutaneous α5(IV) chain was measured by a confocal laser microscope using an anti-α5(IV) monoclonal antibody. The expression ratio of α5(IV) distribution was quantified dividing the extension of the positive signal and the maximal extension of the specimen. Urinary protein excretion was expressed as urinary protein over urinary creatinine ratio. Results. Proteinuria was present in five of the 22 patients. In two patients with proteinuria, α5(IV)chain was normally distributed; in the remaining three, the expression ratio of α5(IV)-chain was 35%, 47%, and 48%. Of the 17 patients without proteinuria, two displayed a complete absence of the α5(IV) chain in EBM, five displayed a normal staining, and the remaining 10 had an expression ratio between 18% and 65%. Conclusion. Our data suggest that there is no correlation between the severity of the glomerular involvement (expressed by proteinuria) and the staining of the α5 chain in the EBM in females with X-linked Alport syndrome.