Impaired high-density lipoprotein function and endothelial barrier stability in severe anaphylaxis - 23/05/24

Doi : 10.1016/j.jaci.2024.03.031

Sergio Fernandez-Bravo, MSc ^a, Marina Canyelles, PhD ^b,^c, Ariadna Martín-Blázquez, MSc ^a, Carla Borràs, MSc ^b,^c, Emilio Nuñez-Borque, PhD ^a, Lucia Palacio-García, MSc ^a, Pablo Rodríguez Del Rio, MD, PhD ^d, Diana Betancor, MD ^e, Alicia Gómez-López, MD ^e, Marina Sabaté Brescó, PhD ^f,^g, José Julio Laguna, MD ^h, Nerea Méndez-Barbero, PhD ^i,^j, Noemi Rotllan, PhD ^b,^c, Joan Carles Escolà-Gil, PhD ^b,^c, Vanesa Esteban, PhD ^a,^j,^⁎
^a Department of Allergy and Immunology, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
^b Institut de Recerca de l’Hospital Santa Creu i Sant Pau, Institut d’Investigacions Biomèdiques Sant Pau, Barcelona, Spain
^c CIBER of Diabetes and Related Metabolic Diseases, Instituto de Salud Carlos III, Madrid, Spain
^d Allergy Department, Hospital Infantil Universitario Niño Jesús, Fundación HNJ, Health Research Institute–Princesa, Madrid, Spain
^e Department of Allergy. Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (FJD, UAM), Madrid, Spain
^f Department of Allergy and Clinic Immunology, Clínica Universidad de Navarra, and Red de Enfermedades Inflamatorias (RD21/0002/0028), Pamplona, Spain
^g Health Research Institute (IDISNA, Instituto de Investigación Sanitaria de Navarra), Pamplona, Spain
^h Allergy Unit, Allergo-Anaesthesia Unit, Cruz Roja Central Hospital, and Red de Enfermedades Inflamatorias (RD21/0002/0008), Madrid, Spain
ⁱ Vascular Pathology Research Laboratory, Health Research Institute–Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
^j Faculty of Medicine, Universidad Alfonso X el Sabio (UAX), Villanueva de la Cañada, Spain

^∗Corresponding author: Vanesa Esteban, PhD, Department of Allergy and Immunology, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain.Department of Allergy and ImmunologyIIS-Fundación Jiménez Díaz, UAMMadridSpain

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Graphical abstract

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Abstract

Background

Growing evidence demonstrates the importance of high- and low-density lipoprotein cholesterol in certain immune and allergy-mediated diseases.

Objective

This study aimed to evaluate levels of high- and low-density lipoprotein cholesterol and apolipoproteins A1 and B in sera 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.

Methods

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 sera, and we also evaluated macrophage cholesterol efflux in response to the serum samples. Last, the effect of anaphylactic-derived high-density lipoprotein (HDL) particles on the endothelial barrier was studied. Detailed methods are provided in the Methods section in this article’s Online Repository available at www.jacionline.org.

Results

Serum samples from severe anaphylactic reactions show statistically significant low levels of HDL cholesterol, low-density lipoprotein cholesterol, and apolipoproteins A1 and B, which points to their possible role as biomarkers. Specifically, HDL particles play a protective role in cardiovascular diseases. Using functional human serum cell assays, we observed impaired capacity of apolipoprotein B–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.