Immunology and biochemistry of normal and diabetic renal basement membrane.

Diabetic and normal glomerular basement membranes have been examined chemically and immunologically for differences which could be pathognomonic of diabetes mellitus. Kidneys were obtained at post-mortem from diabetic subjects, normal subjects over sixty years and also from normal subjects under thirty years following fatal road accidents. Solubilisation of isolated glomeruli was effected by (a) enzymic digestion using collagenase and (b) chaotropic reagents; the solubilised components were identified by immunoelectrophoresis and polyacrylamide gel electrophoresis. A similarity of the antigenic components between all three groups was noted. Carbohydrate analysis of the glomerular basement membranes from diabetic and old normal groups aged above sixty years showed a decrease in sialic acid and glucose content with an associated increase in hexosamine, galactose and total hexose when compared with normal subjects aged below thirty years. The molar ratio of galactose/glucose was higher in the diabetic and old normal groups which, since the ratio of galactose to hydroxylysine was similar in all groups, indicates an increased number of hydroxylysine/galactose residues in diabetics and old normals. Amino acid analyses of glomeruli showed an increase in hydroxylysine, glycine and proline in diabetic and old normal groups only and there was also an associated decrease in lysine and histidine. The diabetic kidney was studied for the presence of antibody to basement membrane using immunofluorescence. The results showed an inherent fluorescence in diabetic and old normal kidneys and a deposition of immunoglobulin in some diabetic kidneys. Diabetic sera were also investigated using indirect immunofluorescence, but no antibody was detected. Further, leucocytes from diabetic patients were investigated in vitro for a cell-mediated response to basement membrane antigens using the leucocyte migration inhibition test. Inhibition of migration was not detected either with normal or diabetic glomerular basement membrane. The differences observed between diabetic and young normal glomeruli could be due to an acceleration of processes associated with age. In the light of the present findings investigation of the chemical and immunological differences between glomeruli from juvenile diabetics and young normal glomeruli should prove interesting