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 me mbrane (EBM) of 23 families with hereditary nephritis was examined by indirect immunofluorescence. These families were divided into three cl inicopathological groups. Group I (10 families) patients showed a wide spread ''basket weave'' pattern of the GBM and a family history of nep hritis 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 b ut no ''basket weave'' change, and had a family history of nephritis a nd chronic renal failure. alpha 1(IV) and alpha 2(IV) were present in all affected and unaffected family members and controls. All normal fa mily 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 complet e loss of the alpha 5(IV) antigen from the GBM and EBM in male patient s, and segmental loss of the alpha 5(IV) antigen in female patients. I n these families the (alpha 3(IV) and alpha 4(IV) antigens were comple tely lost from the GBM in male patients with severe nephritis, whereas alpha 3(IV) and alpha 4(IV) were present but diminished in male patie nts with mild nephritis. Three group II and all group III families exp ressed the alpha 3-5(IV) antigens in an identical manner to that of no rmal controls. These findings indicate that the heterogeneity of hered itary 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 syn drome.