Immunohistochemical study of alpha 1-5 chains of type IV collagen in hereditary nephritis.

The distribution of alpha 1-5 chains of type IV collagen [alpha 1-5(IV)] in the glomerular basement membrane (GBM) and epidermal basement membrane (EBM) of 23 families with hereditary nephritis was examined by indirect immunofluorescence. These families were divided into three clinicopathological groups. Group I (10 families) patients showed a widespread "basket weave" pattern of the GBM and a family history of nephritis was present. Group II (6 families) patients showed a widespread "basket weave" change without a family history of nephritis. Group III (7 families) patients showed a widespread attenuation of the GBM but no "basket weave" change, and had a family history of nephritis and chronic renal failure. alpha 1(IV) and alpha 2(IV) were present in all affected and unaffected family members and controls. All normal family members and controls expressed alpha 3(IV), alpha 4(IV) and alpha 5(IV) in the GBM and alpha 5(IV) in the EBM in a diffuse pattern. All group I families and three of the group II families exhibited complete loss of the alpha 5(IV) antigen from the GBM and EBM in male patients, and segmental loss of the alpha 5(IV) antigen in female patients. In these families the alpha 3(IV) and alpha 4(IV) antigens were completely lost from the GBM in male patients with severe nephritis, whereas alpha 3(IV) alpha 4(IV) were present but diminished in male patients with mild nephritis. Three group II and all group III families expressed the alpha 3-5(IV) antigens in an identical manner to that of normal controls. These findings indicate that the heterogeneity of hereditary nephritis reflects a variety of aberrant expression patterns of alpha 3-5(IV) and that immunohistochemical examination of alpha 5(IV) in the EBM is a useful method for the diagnosis of X-linked Alport syndrome.