Immunoglobulin isotypes in the circulating immune complexes of diabetic rats with and without proteinuria: A chronological study

Circulating immune complexes (CIC) have been postulated to contribute to the development of the secondary complications of diabetes mellitus. Therefore studies were performed to determine whether CIC are the cause of the consequence of the development of diabetic nephropathy. This was done by comparing the occurrence and concentration of CIC containing the different isotypes of immunoglobulins in control rats to those detected in streptozotocin-induced (Sz) diabetic rats that developed albuminuria (Group I) and that did not develop albuminuria (Group II). Only CIC containing IgM, IgG2b and IgG2c were detected in diabetic rats. By staging Group I albuminuric diabetic rats to a clinical reference point of albuminuria, there was no correlation between the occurrence or concentration of CIC containing any isotype of immunoglobulin and the onset of albuminuria. In all Group I albuminuric diabetic rats, the occurrences of all CIC were variable and their concentrations fluctuated during the development and early progression of nephropathy. However, after this group of diabetic rats progressed to overt nephropathy (marked by albuminuria and IgG proteinuria), CIC could be demonstrated in 100% of the animals. In diabetic rats that did not develop albuminuria (Group II), CIC containing IgG2b occured earlier and more often that in Group I albuminuric rats. Similarly, the subclass IgG2c were detected in the CIC of Group II non-albuminuric rats more frequently and in higher concentrations than in Group I albuminuric rats. CIC containing IgM were detected in all 3 animal groups, however, in higher concentrations and occurrences in Group II non-albuminuric rats as compared to control and Group I albuminuric rats. The consistent elevation in CIC after the development of diabetic nephropathy, suggests that the CIC containing any immunoglobulin isotype either result from diabetic kidney, or from other deteriorating conditions associated with the diabetic state. The data also suggests that CIC are not involved in the onset or progression of diabetic nephropathy regardless of the isotypes of immunoglobulins contained within the CIC. However, there is an isotypic restriction in the immunoglobulins detected in the CIC of diabetic rats (IgM, IgG2b and IgG2c) that may signal some involvement of the immune system in the development of diabetic nephropathy.