Immunohistochemical Study for the Diagnosis of Alport’s Syndrome
Pimpong Wongtrakul MD*, Chairat Shayakul MD*, Paisal Parichatikanond MD**, Puan Suthipinittharm MD***, Chalongrat Amjaroen MS*, Naparat Kaewkaukul MSc*, Arun Vongirad MD****, Leena Ongajyooth MD*
Affiliation : * Renal Division, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University **Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University *** Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University **** Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University
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.
Materials and Methods : 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 sus-
pected of AS, as it is much less invasive. Moreover, it is a useful adjunct to conventional examination of
biopsied renal tissue.
Keywords : Alport’s syndrome, Hereditary nephritis, Collagen type IV, Immunohistochemistry
