Hereditary nephritis (Alport syndorome) : abnormalities in type IV collagen alpha5 chain and skin diagnosis

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To identify the abnormalities of the type IV collagen alpha5 chain, alpha5 (IV), in Alport syndrome, we examined renal and skin tissues using rat monoclonal antibodies recognizing non-consensus amino acid sequences of alpha5 (IV). Immunofluorescence of normal human kidney and skin tissues revealed linear alpha5 (IV) staining in the basement membrane (BM) of glomerulus, Bowman's capsule, in some tubules and also in the epidermal BM.Renal specimens from 5 male patients of 4 families with X-linked Alport syndrome showed no reactivity for alpha5 (IV) in glomerulus, Bowman's capsules and tubules. In these patients, alpha1 (IV) and alpha2 (IV) were normal, whereas alpha3 (IV), alpha4 (IV), alpha5 (IV) and alpha6 (IV) were absent from the BMs of the kidney. In skin tissues of male patients, neither alpha5 (IV) nor alpha6 (IV) were detected. The epidermal BM of female heterozygotes with X-linked Alport syndrome showed a mosaic staining for alpha5 (IV) and alpha6 (IV). These findings indicate that, in addition to a disturbed alpha3 (IV) -alpha4 (IV) -alpha5 (IV) network, patients with X-linked Alport syndrome have abnormalities in alpha6 (IV) of the renal and epidermal BMs at the protein level.