Immunohistochemical study for the diagnosis of Alport's syndrome

Abstract

Background: Alport's syndrome (AS) is the most common cause of inherited glomerular disease in Thailand. The majority of cases show X-linked inheritance, which is caused by mutations in the gene coding for the α5 chain of type IV collagen in the glomerular basement membrane (GBM) and epidermal basement membrane (EBM). Such mutation usually leads to a reduction in protein amount, thus, immunohistochemical studies have been considered in diagnostic evaluation. Objective: To study the expression of α[IV] collagen chains in the skin as an alternative approach to diagnose AS. Material and Method: Eleven unrelated probands with proven AS, 7 relatives with abnormal urinalysis, 4 suspected individuals, and 8 normal controls were enrolled. A punch skin biopsy and immunofluorescence staining of the tissue specimens for α1, α3 and α5[IV] collagen chains was performed. Results: The α5[IV] chain was absent in the EBM in all male AS patients while a discontinuing pattern was observed in all females except one. The findings are specific for AS with a sensitivity of 91%. Studies in relatives and suspected individuals also confirmed the advantage of this approach as demonstrated by the absence and discontinuation of α5[IV] staining in all males and females, respectively. We also analyzed their expressions in the kidney tissue and demonstrated abnormal α3 and α5[IV] staining in five of six samples. Conclusion: Immunohistochemical study of the skin should be used as a screening method in patients suspected of AS, as it is much less invasive. Moreover, it is a useful adjunct to conventional examination of biopsied renal tissue.