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An ELISA was used to measure the fluid-phase complement complex in the plasma of 54 patients with insulin-dependent (type I) diabetes mellitus. Sixty-seven per cent of the diabetic patients had increased levels of SC5b-9. In individual diabetic patients, increased SC5b-9 was found to be significantly associated with the occurrence of anti-heparan sulphate cross-reactive anti-ssDNA antibodies and in some cases with circulating immune complexes. There was a significant correlation between levels of SC5b-9 and those of urinary albumin excretion rate (AER) (r = 0.39, P less than 0.01). Levels of AER were 8.4 +/- 2.26 micrograms/min and 2.04 +/- 0.35 micrograms/min in the SC5b-9 positive and negative patients, respectively (P less than 0.01). A relationship was also found between SC5b-9 and plasma von Willebrand Factor (r = 0.45, P less than 0.02), von Willebrand factor was 189.2 +/- 19.3% and 132.3 +/- 19.6% in SC5b-9 positive and negative patients, respectively (P less than 0.05). It may be that the abnormalities found in this study play a role in the pathogenesis of the late diabetic vascular complications.

C3 fixing IgA immune complexes were found to be elevated in 25% of patients with type 2 (non insulin-dependent) diabetes mellitus as compared to healthy subjects (2%). Immune complexes containing both IgA and IgG were found in 42% of the diabetic population but not in controls. The presence of C3-IgA and/or IgA/IgG immune complexes correlated with the occurrence of antiglobulins antibodies of IgA class in particular with autoantibodies reactive with the Fab2 portion of IgG. These immunopathological findings were more frequent in patients that exhibited microvascular complications and in particular in patients with proliferative retinopathy. These and our previous results strongly suggest a role of IgA system abnormality in the pathogenesis of diabetic vascular complications.

Anti-single-stranded-DNA antibodies cross-reactive with heparan sulfate were detected in serums of patients with type I (insulin-dependent) diabetes mellitus. The results suggested that heparan sulfate, the major glycosaminoglycan constituent of the glomerular basement membrane, may serve as a target antigen in vivo for cross-reactive anti-DNA antibodies. These polyreactive antibodies, directed toward repeating negatively charged units, may neutralize the heparan sulfate-associated polyanionic sites in the glomerulus, leading to an abnormal permeability of anionic plasma proteins.

IgA and IgG antibodies against cardiolipin and/or phosphatidylserine were detected in the sera of patients with non insulin-dependent (type 2) diabetes mellitus. The highest prevalence was observed in particular in patients with macrovascular complications (86%). A significant increase of platelet bound IgA and IgG was observed also in patients with sera positive for anti-phospholipid antibodies suggesting the coexistence of reactivity against phospholipid and platelets. Several reports have focused on a new clinical entity characterized by the presence of anti-phospholipid and by a tendency to venous and arterial thrombosis. In addition to their acute thrombogenic effects, we suggest that anti-phospholipid antibodies may play a role in the impairment of the thromboresistant property of vascular endothelium and in the enhancement of platelet aggregation leading to the pathogenesis and/or progression of the macrovascular diabetic complications.