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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.

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.