A cause of falsely low HDL concentrations in HIV-infected patients: increased polyclonal serum immunoglobulin

Objective: To describe the interference of polyclonal hypergammaglobulinemia in a direct HDL-c method. Methods: HDL-c was measured by a direct method (Roche Diagnostics) in four HIV-infected patients showing polyclonal hypergammaglobulinemia and also by precipitation with phosphotungstic acid and ultracentrifugation at a density of 1.063 kg/L. In addition, an electrophoretic lipid profile was performed by an automated electrophoretic system. Results: Direct HDL-c concentration was very low or even nondetectable in all hyperglobulinemic samples. Ultracentrifugation showed a higher HDL-c concentration, and the electrophoretic lipid profile showed a band corresponding to HDL particles whose cholesterol concentration was in concordance with that of ultracentrifugation. Kinetic monitoring of the absorbance for the direct HDL-c method showed a high reading after the first reagent addition and a final absorbance quite close to or even lower than the initial absorbance. Conclusion: Although interference by any HIV therapy drug cannot be completely ruled out, our results showed that when high immunoglobulin concentrations existed in the patientʹs serum, the direct HDL-c method yielded low or undetectable HDL-c values. The high initial absorbance observed suggested an interaction between immunoglobulins and the first reagent of the method, producing a complex that scattered light and falsely decreased HDL-c concentrations.