COLLAGEN DISTRIBUTION IN FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS - AN IMMUNOFLUORESCENCE AND ULTRASTRUCTURAL IMMUNOGOLD STUDY

Focal and segmental glomerulosclerosis (FSGS) is a non-specific scarri ng process of the glomerulus, initially described in idiopathic nephro tic syndrome. The distribution of types I, III, IV, V, and VI collagen and of the alpha 1, alpha 3, alpha 4, alpha 5, and alpha 6 chains of type IV collagen was studied by immunohistochemistry in sclerotic lesi ons of nine nephrotic children. Dual immunofluorescence and high-resol ution immunogold labelling were used to determine the precise distribu tion of the antigens. No changes were detected in normal glomeruli of patients compared with controls. In FSGS, type IV collagen [alpha 1(IV )2 alpha 2(IV)], and to a lesser degree type VI, accumulates in the tw o components of the lesion: the enlarged mesangial matrix and the mate rial deposited between the pushed-out podocytes and the alpha 3-alpha 5(IV)-positive glomerular basement membrane. Staining for alpha 6(IV) and types I, III, and V collagen was practically negative. These resul ts suggest that the matrix components of the sclerotic lesion are prod uced solely by glomerular cells. Changes in the relative distribution of type IV collagen chains, characterized by the presence of collagen [alpha 1(IV)2 alpha 2(IV)] in close contact with the podocytes, strong ly suggest a switch in the podocyte programme of collagen synthesis.