Assessment of the role of the immunoglobulin isotypes in the development of diabetic nephropathy in untreated streptozotocin-induced diabetic rats.
Thirty of 45 (67%) streptozotocin-induced male Sprague-Dawley diabetic rats developed microalbuminuria that progressed to overt proteinuria with increased concentrations of IgG in their urine. 33% (15/45) never developed albuminuria or IgG proteinuria. These percentages did not correlate with glucose control since none of the animals were treated with insulin and all demonstrated the same degree of hyperglycemia. Indirect immunofluorescent antibody staining of frozen tissue sections from the kidneys of rats that developed overt proteinuria stained for IgM (67%), C3 (93%), IgG2b (93%) and IgG2c (60%). Non-proteinuric diabetic kidneys stained for IgM (80%), C3 (67%) IgG2b (67%) and IgG2c (87%). Control kidney sections demonstrated no consistent staining pattern. The occurrence and concentration of the different immunoglobulin isotypes, eluted from frozen sections with immune complex dissociating buffers, mimicked that which was observed by immunofluorescence. When urine or serum from the same rat or a rat of a different group was incubated with kidney sections eluted of all immunoglobulin, indirect immunofluorescent staining demonstrated antibody activity corresponding to the original staining pattern observed for each animal group prior to elution. The most consistent observation was that the diabetic rats that developed proteinuria were positive for IgG2b staining in their kidney sections; whereas, those that did not develop proteinuria stained predominantly for IgG2c. From this data, we suggest that the progression of diabetic nephropathy may depend on whether a specific IgG subclass response is elicited.
Thiele
G M
GM
University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha 68105.
McDonald
T L
TL
D000818:Animals; D003176:Complement C3 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D007074:Immunoglobulin G / Q000378:metabolism* / Q000652:urine; D007075:Immunoglobulin M / Q000378:metabolism / Q000652:urine; D007668:Kidney / Q000276:immunology; D008297:Male; D011507:Proteinuria / Q000209:etiology / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains
D003176:Complement C3; D007074:Immunoglobulin G; D007075:Immunoglobulin M