Immunohistochemical study of α1-5 chains of type IV collagen in hereditary nephritis

Abstract

The distribution of (α1-5 chains of type IV collagen [α1-5(IV)] in the glomerular basement membrane (GEM) 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 GEM 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 GEM but no 'basket weave' change, and had a family history of nephritis and chronic renal failure. α1(IV) and α2(IV) were present in all affected and unaffected family members and controls. All normal family members and controls expressed α3(IV), α4(IV) and α5(IV) in the GEM and α5(IV) in the EBM in a diffuse pattern. All group I families and three of the group II families exhibited complete loss of the α5(IV) antigen from the GEM and EBM in male patients, and segmental loss of the (US(IV) antigen in female patients. In these families the α3(IV) and α4(IV) antigens were completely lost from the GEM in male patients with severe nephritis, whereas α3(IV) and α4(IV) were present but diminished in male patients with mild nephritis. Three group II and all group III families expressed the α3-5(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 α3-5(IV) and that immunohistochemical examination of α5(IV) in the EBM is a useful method for the diagnosis of X-linked Alport syndrome.