ANTI-MODIFIED LDL ANTIBODIES AND LDL-CONTAINING IMMUNE-COMPLEXES IN IDDM PATIENTS AND HEALTHY CONTROLS

Antibodies to oxidized LDL (ox-LDL) and LDL containing immune complexe s (LDL-IC) have been reported to be associated with the presence or pr ogression of arteriosclerosis. We screened for anti-modified LDL antib odies and isolated soluble IC by precipitation with 3.5% (w/v) polyeth ylene glycol (PEG) 6000 in two groups. The patient group was constitut ed by 16 insulin-dependent diabetes mellitus subjects free of macrovas cular complications. The control group was constituted by 16 healthy, age-, gender-, race-, and body mass index-matched nondiabetic subjects . We detected anti-ox-LDL antibodies and anti-malondialdehyde-modified LDL antibodies with similar levels in patients and controls, while th e levels of anti-glycated LDL antibodies were very low, but slightly h igher in diabetics than in healthy controls. Isolated LDL-IC were adso rbed to red blood cells (RBC) and incubated with human macrophages for 18 hr at 37 degrees C. Under those experimental conditions, RBC-adsor bed IC are taken up by macrophages but the RBC remain intact and are n ot ingested. Slightly higher levels of cholesteryl ester (CE) accumula tion were measured in macrophages incubated with RBC to which we adsor bed IC isolated from diabetics (15.4 +/- 2.5 mu g/mg of protein, mean +/- SEM) than in macrophages incubated with IC isolated from controls (12.5 +/- 1.6 mu g/mg of protein, mean +/- SEM), but the difference di d not reach statistical significance. PEG-precipitable IC isolated fro m both normal and diabetic subjects led, in some instances, to the tra nsformation of macrophages into foam cells. Significant correlations w ere observed between CE accumulation and the content of apo B (P < 0.0 001), total cholesterol (P = 0.0004), IgG (P = 0.015), and IgA (P = 0. 015) in the isolated IC. The correlation between CE accumulation and t he content of apo B in isolated IC was stronger in diabetics than in t he control group (r = 0.759 vs r = 0.500). Fractionation of isolated I C in immobilized protein A/G yielded immunoglobulin-rich fractions whi ch contained cholesterol and IgG anti-ox-LDL antibodies. The cholester ol content of these fractions was significantly correlated (P = 0.001) with CE accumulation. In conclusion, both diabetics and normal indivi duals have circulating IC whose atherogenic potential appears to be re lated to the presence of LDL and antibodies of the IgG and IgA isotype s. (C) 1997 Academic Press.