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

Focal and segmental glomerulosclerosis (FSGS) is a non-specific scarring process of the glomerulus, initially described in idiopathic nephrotic syndrome. The distribution of types I, III, IV, V, and VI collagen and of the α1, α3, α4, α5, and α6 chains of type IV collagen was studied by immunohistochemistry in sclerotic lesions of nine nephrotic children. Dual immunofluorescence and high-resolution immunogold labelling were used to determine the precise distribution of the antigens. No changes were detected in normal glomeruli of patients compared with controls. In FSGS, type IV collagen [α1(IV)2 α2(IV)], and to a lesser degree type VI, accumulates in the two components of the lesion : the enlarged mesangial matrix and the material deposited between the pushed-out podocytes and the α3-α5(IV)-positive glomerular basement membrane. Staining for α6(IV) and types I, III, and V collagen was practically negative. These results suggest that the matrix components of the sclerotic lesion are produced solely by glomerular cells. Changes in the relative distribution of type IV collagen chains, characterized by the presence of collagen [α1(IV)2 α2(IV)] in close contact with the podocytes, strongly suggest a switch in the podocyte programme of collagen synthesis.