SCREENING FOR FAMILIAL DEFECTIVE APOLIPOPROTEIN-B-100 WITH IMPROVED U937 MONOCYTE PROLIFERATION ASSAY

Frostegard et al. (J Lipid Res 1990;31:37-44) demonstrated that the pr oliferation of the human monocyte cell line U937 is critically depende nt on the uptake of low-density lipoprotein (LDL) via the apo B,E (LDL ) receptor, a characteristic that was used to detect patients with fam ilial defective apolipoprotein B-100 (FDB). Here we applied this princ iple to develop a simple and reproducible assay for the detection of p atients with functionally defective LDL. We added serum to U937 cells in cholesterol-free incubation medium and determined the increase in c ell number after a 72-h incubation at 37-degrees-C by using an electro nic cell counter. Sera from 10 normolipidemic individuals and from 34 patients with type IIa hyperlipoproteinemia stimulated the growth of U 937 cells in proportion to the exogenous cholesterol concentration (r = 0.83, P <0.001) and the LDL-cholesterol concentration (r = 0.81, P < 0.001). However, sera from 16 patients with FDB stimulated less cell p roliferation than did sera from patients with type IIa hyperlipoprotei nemia with equal LDL-cholesterol concentrations. With a 15% reduction in growth as the cutoff value, this test had a sensitivity and specifi city for diagnosis of FDB of 87.5% and 100%, respectively. The improve d U937 monocyte proliferation assay can be used for screening hypercho lesterolemic patients to detect individuals with functionally defectiv e LDL.