Testing
New assay reveals Lp(a) particles are 4-fold richer in triglycerides in hypertriglyceridemia, method study of 150 (J Lipid Res 2026)
Original title: A novel immune-isolation method for direct quantification of triglycerides associated with lipoprotein(a)
Development and validation of a novel immune-isolation assay (monoclonal antibody LPA4) for direct quantification of Lp(a)-associated triglycerides (Lp(a)-TG), applied to 36 normotriglyceridaemic individuals and 114 with moderate hypertriglyceridaemia (150-500 mg/dL). In normotriglyceridaemic individuals, mean Lp(a)-TG was 1.42 mg/dL and Lp(a)-cholesterol (Lp(a)-C) 4.03 mg/dL (Lp(a)-TG/Lp(a)-C ratio 0.59), together accounting for 1.22% of total plasma triglycerides and 2.62% of total plasma cholesterol. In hypertriglyceridaemic individuals, mean Lp(a)-TG rose to 53.7 mg/dL and Lp(a)-C to 14.4 mg/dL (ratio 3.99), together accounting for 19.9% of plasma triglycerides and 9.68% of plasma cholesterol. The authors conclude this is the first validated, high-throughput assay for direct Lp(a)-TG quantification, demonstrating that Lp(a) lipid composition is variable and becomes enriched in both triglycerides and cholesterol in hypertriglyceridaemic states, providing a platform for future mechanistic and pharmacologic studies.
Original abstract
Lipoprotein (a) [Lp(a)] is viewed as a cholesterol-rich, LDL-like particle, yet potential heterogeneity in its lipid composition is not well understood. We developed and validated a novel immune-isolation assay to directly quantify triglycerides (TGs) associated with Lp(a) [Lp(a)-TGs]. Lp(a) was selectively isolated from plasma using magnetic beads conjugated with monoclonal antibody LPA4 targeting apolipoprotein(a), followed by enzymatic quantification of TGs. Assay specificity was ensured using washing buffers to prevent nonspecific lipoprotein interactions. Spike-in experiments with purified VLDL/intermediate density lipoprotein lacking Lp(a) demonstrated no measurable interference. Lp(a)-cholesterol [Lp(a)-C] was measured using an established immune-isolation method. The ratio of Lp(a)-TG to Lp(a)-C was calculated to distinguish TG-enriched Lp(a) particles from the typical cholesterol-rich, LDL-like phenotype. Lp(a)-TG, Lp(a)-C, Lp(a) molar concentration, and estimated compositional ratios were quantified in 36 normotriglyceridemic individuals and 114 individuals with moderate hypertriglyceridemia (150-500 mg/dl). In normotriglyceridemic individuals, mean (SD) TGs were 98.4 (31.9) mg/dl, Lp(a)-TG 1.42 (2.83) mg/dl, Lp(a)-C 4.03 (4.01) mg/dl, and the Lp(a)-TG/Lp(a)-C ratio was 0.59 (1.27). Lp(a)-TG and Lp(a)-C accounted for mean (SD) 1.22% (0.10) of total plasma TGs and 2.62% (2.01) of total plasma cholesterol. In individuals with hypertriglyceridemia, mean (SD) TGs were 284 (85) mg/dl, Lp(a)-TG 53.7 (25.3) mg/dl, Lp(a)-C 14.4 (6.9) mg/dl, and the Lp(a)-TG/Lp(a)-C ratio was 3.99 (1.20). Lp(a)-TG and Lp(a)-C accounted for mean (SD) 19.9% (6.53) of total plasma TGs and 9.68% (4.41) of total plasma cholesterol. This immune-isolation assay is the first validated, high-throughput method for direct quantification of Lp(a)-TG. This study demonstrates that Lp(a) lipid composition is variable and enriched in triglycerides and cholesterol in hypertriglyceridemic states. It provides a platform for future mechanistic, epidemiologic, and pharmacologic studies of Lp(a)-triglyceride interactions. This immune-isolation assay is the first validated, high-throughput method for direct quantitation of Lp(a)-TG.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.