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 (α-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.
Increased Plasma IgA, sIgA, and C3- and IgA-Containing Immune Complexes With Renal Glomerular Deposits in Diabetic Rats
Leon L Miller, Mary Jane Izzo, Drusilla Wemett, Bernard J Panner, Eric A Schenk; Increased Plasma IgA, sIgA, and C3- and IgA-Containing Immune Complexes With Renal Glomerular Deposits in Diabetic Rats. Diabetes 1 February 1988; 37 (2): 185–193. https://doi.org/10.2337/diab.37.2.185
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