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Autoimmunity and inflammation are associated with marked changes in lipid and lipoprotein metabolism in SLE. Autoantibodies and cytokines are able to modulate lipoprotein lipase (LPL) activity, a key enzyme in lipid metabolism, with a consequent "lupus pattern" of dyslipoproteinemia characterized by elevated levels of very low-density lipoprotein cholesterol (VLDL) and triglycerides (TG) and lower high-density lipoprotein cholesterol (HDL) levels. This pattern favors an enhanced LDL oxidation with a subsequent deleterious foam cell formation. Autoantibodies and immunocomplexes may aggravate this oxidative injury by inducing accumulation and deposition of oxLDL in endothelial cells. Drugs and associated diseases usually magnify the close interaction of these factors and further promote the proatherogenic environment of this disease.

Bacterial endotoxin (i.e., lipopolysaccharide [LPS]) elicits dramatic responses in the host, including elevated plasma lipid levels due to increased synthesis and secretion of triglyceride-rich lipoproteins by the liver and inhibition of lipoprotein lipase. This cytokine-induced hyperlipoproteinemia, clinically termed the "lipemia of sepsis," was customarily thought to involve the mobilization of lipid stores to fuel the host response to infection. However, because lipoproteins can also bind and neutralize LPS, we have long postulated that triglyceride-rich lipoproteins (very-low-density lipoproteins and chylomicrons) are also components of an innate, nonadaptive host immune response to infection. Recent research demonstrates the capacity of lipoproteins to bind LPS, protect against LPS-induced toxicity, and modulate the overall host response to this bacterial toxin.

The mechanism of severe hyperlipidemia in a 54-year-old woman with multiple myeloma and monoclonal immunoglobulin A (IgA) gammopathy was investigated. Her plasma total cholesterol and triglyceride concentrations were 29.7 mmol/l (1,150 mg/dl) and 11.9 mmol/l (1,060 mg/dl), respectively. Western blot analysis demonstrated that her low density lipoproteins (LDL) contained IgA. This IgA also was shown to bind to control LDL and inhibited 125I-LDL binding to fibroblasts, suggesting that by binding to the LDL, IgA interfered with LDL binding to LDL receptors. These findings indicate that an inhibitory monoclonal IgA against LDL binding may explain, at least in part, the severe hyperlipidemia observed in this case.

Objective: To determine the influence of systemic lupus erythematosus (SLE), disease activity, and anticardiolipin antibodies (aCL) on lipid profile, in order to identify patients with high risk for coronary artery disease (CAD)., Methods: Fasting lipid profiles were performed in 36 consecutive female SLE patients without any therapy and 30 controls. Exclusion criteria were diabetes mellitus, CAD, liver or thyroid disease, ingestion of lipid-raising drugs, serum creatinine > or = 1.5 mg/dl, and proteinuria > or = 0.5 g/d. Disease activity was measured by SLEDAI., Results: High levels of VLDL-C and TG and low levels of HDL-C, the 'lupus pattern', were observed in inactive SLE compared to controls (P < 0.05). Active disease enhanced this difference inducing a more striking increase in VLDL-C and TG levels and also a decrease in HDL-C and LDL-C levels compared to inactive SLE patients (P < 0.05), characterizing the 'active lupus pattern'. Moreover, a significant correlation was found between SLEDAI scores and all lipid fractions. Furthermore these lipid abnormalities were particularly associated with vasculitis. Lower HDL-C levels detected in IgG aCL+ patients compared to IgG aCL- patients were not confirmed by two-way analysis of variance which demonstrated that this difference was exclusively caused by disease activity., Conclusions: Our findings suggest that SLE patients have a lipid profile abnormality which is aggravated by disease activity and may reside in a defect of VLDL metabolism. This pattern of dyslipoproteinemia may increase the risk of developing coronary artery disease.

Impairment of fibrinolysis is supposed to contribute to CVD. In 38 hyperlipoproteinemic patients, known to be at risk for early CVD, fibrinolytic activity was measured before and after stimulation with DDAVP. A negative correlation was found between serum triglyceride levels and fibrinolytic activity, both before and after DDAVP. A subnormal activity was invariably found when serum triglyceride concentration was above 8 mmol/L. The defect can be attributed to low levels of extrinsic plasminogen activator. High cholesterol levels were not associated with impairment of fibrinolysis. Fibrinolytic activity and response to DDAVP were lowest in those patients with hypertriglyceridemia who also had a tendency to develop hyperchylomicronemia. (type V/IV). The low fibrinolytic activity in this type of hyperlipoproteinemia cannot be explained by obesity. Factor VIII was higher than normal in most patients with hyperlipoproteinemia; the level increased after stimulation with DDAVP in every patient. This imbalance between coagulation and fibrinolysis might increase the risk of CVD.

Using immunological and biochemical methods, the existence was proved of a relationship between atherogenous types of hyperlipoproteinaemia and decrease of the functional activity of the T-component of the immune system in patients with ischaemic heart disease. In IHD patients without lipid metabolism disturbances the indicators of the functional activity of the thymus-dependent factor of the immune system were reduced to a much lesser extent. The results stress the role of thymus-dependent factors and lipids in the development of ischaemic heart disease.

In a study of the immunoglobulin concentrations in an urban population and in patients with hyperlipoproteinemia we observed significant positive correlations between serum triglycerides and IgA independent of sex, age and body weight. In men serum triglycerides also correlated with IgG and IgM, and serum cholesterol with IgA. The prevalence of hyper- and hypoimmunoglobulinemia was significantly higher in hyperlipidemic than in normolipemic subjects. We propose that the occurrence of hyperlipoproteinemia with hypoimmunoglobulinemia may be caused by different pathobiological mechanisms than the occurrence with hyperimmunoglobulinemia.

When compared to values obtained in normalweight, normolipidemic control subjects, the level of complement C3 protein and total complement activity (CH50) were found to be obviously decreased in patients with decompensated cirrhosis of the liver and slightly but significantly increased in subjects with type IIb and type IV hyperlipoproteinemia. C3 protein level was positively correlated with the concentration of serum cholesterol, the logarithm of serum triglyceride concentration, serum pseudocholinesterase and total complement activity. There were no significant differences concerning C3 protein level between hyperlipidemic subjects with clinical atherosclerosis and those without documented vascular disease. It is suggested that accelerated lipoprotein turnover occurring in many subjects with type IIb and type IV hyperlipoproteinemia might enhance the synthesis of several liver produced plasma enzymes and proteins including the C3 protein of the complement system.