Impaired HDL function and endothelial barrier stability in severe anaphylaxis

Abstract

Growing evidence demonstrates the importance of high- and low-density lipoprotein cholesterol in certain immune and allergy-mediated diseases. This study aimed to evaluate levels of high- and low-density lipoprotein cholesterol and apolipoproteins (Apo) A1 and B in serum from a cohort of patients presenting with hypersensitivity reactions. We further assessed the function of high-density lipoprotein particles as well as their involvement in the molecular mechanisms of anaphylaxis. Lipid profile determination was performed in paired (acute and baseline) serum samples from 153 patients. Thirty-eight experienced a non-anaphylactic reaction and 115 had an anaphylactic reaction (88 moderate and 27 severe). Lecithin cholesterol acyl transferase activity was assessed in patient serum, and we also evaluated macrophage cholesterol efflux in response to the serum samples. Lastly, the effect of anaphylactic-derived HDL particles on the endothelial barrier was studied. For detailed Methods, please see the Methods section in this article's Online Repository at www.jacionline.org. Severe anaphylactic reactions show statistically significant low levels of HDL-C, LDL-C, ApoA1, and ApoB, which points to a possible role as biomarkers. Specifically, HDL particles play a protective role in cardiovascular diseases. Using functional human sera-cell assays, we observed an impaired capacity of ApoB-depleted serum to induce macrophage cholesterol efflux in severe anaphylactic reactions. In addition, purified HDL particles from human anaphylactic sera failed to stabilize and maintain the endothelial barrier. These results encourage further research on HDL functions in severe anaphylaxis, which may lead to new diagnostic and therapeutic strategies.