Carolina Perales-Chorda1, David Obeso2,3, Laura Twomey2,3, Ayelén Rojas-Benedicto4, Leonor Puchades-Carrasco4, Marta Roca5, Antonio Pineda-Lucena4,6, José Julio Laguna7,8, Coral Barbas3, Vanesa Esteban8,9, Jaume Martí-Garrido1, Ethel Ibañez-Echevarria1, Ramón López-Salgueiro1, Domingo Barber2, Alma Villaseñor2, Dolores Hernández Fernández de Rojas1. 1. Allergy Department of Hospital, Universitari i Politècnic La Fe, Valencia, Spain. 2. IMMA, Instituto de Medicina Molecular Aplicada, Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe| Boadilla del Monte, Madrid, 28660, Spain. 3. CEMBIO, Centre for Metabolomics and Bioanalysis, Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe| Boadilla del Monte, Madrid, 28660, Spain. 4. Drug Discovery Unit, Health Research Institute La Fe, Valencia, Spain. 5. Analytical Unit, Health Research Institute Hospital La Fe, Valencia, Spain. 6. Molecular Therapeutics Program, Center for Applied Medical Research, University of Navarra, Pamplona, Spain. 7. Allergy Unit, Allergo-Anaesthesia Unit, Hospital Central de la Cruz Roja, Madrid, Spain. 8. Faculty of Medicine and Biomedicine, Alfonso X El Sabio University, Madrid, Spain. 9. Department of Allergy and Immunology, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain.
Abstract
BACKGROUND: Despite the increasing incidence of anaphylaxis, its underlying molecular mechanisms and biomarkers for appropriate diagnosis remain undetermined. The rapid onset and potentially fatal outcome in the absence of managed treatment prevent its study. Up today, there are still no known biomarkers that allow an unequivocal diagnosis. Therefore, the aim of this study was to explore metabolic changes in patients suffering anaphylactic reactions depending on the trigger (food and/or drug) and severity (moderate and severe) in a real-life set-up. METHODS: Eighteen episodes of anaphylaxis, one per patient, were analysed. Sera were collected during the acute phase (T1), the recovery phase (T2) and around 2-3 months after the anaphylactic reaction (T0: basal state). Reactions were classified following an exhaustive allergological evaluation for severity and trigger. Sera samples were analysed using untargeted metabolomics combining liquid chromatography coupled to mass spectrometry (LC-MS) and proton nuclear magnetic resonance spectroscopy (1 H-NMR). RESULTS: 'Food T1 vs T2' and 'moderate T1 vs T2' anaphylaxis comparisons showed clear metabolic patterns during the onset of an anaphylactic reaction, which differed from those induced by drugs, food + drug or severe anaphylaxis. Moreover, the model of food anaphylaxis was able to distinguish the well-characterized IgE (antibiotics) from non-IgE-mediated anaphylaxis (nonsteroidal anti-inflammatory drugs), suggesting a differential metabolic pathway associated with the mechanism of action. Metabolic differences between 'moderate vs severe' at the acute phase T1 and at basal state T0 were studied. Among the altered metabolites, glucose, lipids, cortisol, betaine and oleamide were observed altered. CONCLUSIONS: The results of this exploratory study provide the first evidence that different anaphylactic triggers or severity induce differential metabolic changes along time or at specific time-point, respectively. Besides, the basal status T0 might identify high-risk patients, thus opening new ways to understand, diagnose and treat anaphylaxis.
BACKGROUND: Despite the increasing incidence of anaphylaxis, its underlying molecular mechanisms and biomarkers for appropriate diagnosis remain undetermined. The rapid onset and potentially fatal outcome in the absence of managed treatment prevent its study. Up today, there are still no known biomarkers that allow an unequivocal diagnosis. Therefore, the aim of this study was to explore metabolic changes in patients suffering anaphylactic reactions depending on the trigger (food and/or drug) and severity (moderate and severe) in a real-life set-up. METHODS: Eighteen episodes of anaphylaxis, one per patient, were analysed. Sera were collected during the acute phase (T1), the recovery phase (T2) and around 2-3 months after the anaphylactic reaction (T0: basal state). Reactions were classified following an exhaustive allergological evaluation for severity and trigger. Sera samples were analysed using untargeted metabolomics combining liquid chromatography coupled to mass spectrometry (LC-MS) and proton nuclear magnetic resonance spectroscopy (1 H-NMR). RESULTS: 'Food T1 vs T2' and 'moderate T1 vs T2' anaphylaxis comparisons showed clear metabolic patterns during the onset of an anaphylactic reaction, which differed from those induced by drugs, food + drug or severe anaphylaxis. Moreover, the model of food anaphylaxis was able to distinguish the well-characterized IgE (antibiotics) from non-IgE-mediated anaphylaxis (nonsteroidal anti-inflammatory drugs), suggesting a differential metabolic pathway associated with the mechanism of action. Metabolic differences between 'moderate vs severe' at the acute phase T1 and at basal state T0 were studied. Among the altered metabolites, glucose, lipids, cortisol, betaine and oleamide were observed altered. CONCLUSIONS: The results of this exploratory study provide the first evidence that different anaphylactic triggers or severity induce differential metabolic changes along time or at specific time-point, respectively. Besides, the basal status T0 might identify high-risk patients, thus opening new ways to understand, diagnose and treat anaphylaxis.
Authors: Celia López-Sanz; Rodrigo Jiménez-Saiz; Vanesa Esteban; María Isabel Delgado-Dolset; Carolina Perales-Chorda; Alma Villaseñor; Domingo Barber; María M Escribese Journal: Front Allergy Date: 2022-06-16