Increased plasma IgA, sIgA, and C3- and IgA-containing immune complexes with renal glomerular deposits in diabetic rats.
Male Sprague-Dawley rats were fasted 18 h and given streptozocin (STZ; 60 mg/kg body wt i.p.). The resultant diabetes mellitus, not treated with insulin, was associated with persistent manifoldly increased plasma IgA levels, as measured by single-radial immunodiffusion after reduction with dithiothreitol and alkylation with iodoacetamide. Also observed were concurrent increases in plasma levels of secretory IgA (sIgA) and of C3- and IgA-containing immune complexes (C3-IgA-CIC). After 104 days without insulin treatment, six of the diabetic rats were given daily injections of 2 U of insulin for 11 days. Insulin treatment was associated with a precipitous decrease in plasma levels of IgA, sIgA, and C3-IgA-CIC. Cessation of insulin treatment resulted in restoration of greatly increased levels of all three IgA-containing species. Histoimmunofluorescence studies of kidneys from untreated rats with diabetes of 192-324 days revealed glomerular capillary wall and mesangial deposits reacting strongly with anti-IgA (alpha-chain-specific) antiserum. Kidneys from two of the diabetic rats (324 days) were tested with anti-rat C3 and anti-rat secretory component (SC) antisera, and they reacted positively. Control kidneys from normal rats examined simultaneously were negative. The concurrent changes in plasma levels of three IgA-containing species in the untreated STZ-induced diabetic rat and the demonstration of abnormal immunoreactive IgA-containing renal glomerular deposits make this experiment an attractive model for studying the possible role of disturbed IgA metabolism in the pathogenesis of diabetic nephropathy.
Miller
L L
LL
Department of Biophysics, University of Rochester, New York 14642.
Izzo
M J
MJ
Wemett
D
D
Panner
B J
BJ
Schenk
E A
EA
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis; D003176:Complement C3 / Q000032:analysis / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D005455:Fluorescent Antibody Technique; D007070:Immunoglobulin A / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D007071:Immunoglobulin A, Secretory / Q000032:analysis*; D007328:Insulin / Q000627:therapeutic use; D007668:Kidney / Q000276:immunology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin
D000936:Antigen-Antibody Complex; D001798:Blood Proteins; D003176:Complement C3; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007328:Insulin; D013311:Streptozocin