Rosa Muñoz-Cano1, Mariona Pascal2, Joan Bartra3, Cesar Picado4, Antonio Valero4, Do-Kyun Kim5, Stephen Brooks6, Michael Ombrello6, Dean D Metcalfe5, Juan Rivera7, Ana Olivera5. 1. Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md; Unitat d'Al.lergia, Servei de Neumologia i Al.lergia Respiratoria, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Electronic address: rmunoz@clinic.ub.es. 2. Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Servei d'Immunologia, CDB, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; Spanish Research Network on Adverse Reactions to Allergens and Drugs (RIRAAF: Red de Investigacion de Reacciones Adversas a Alergenos y Farmacos) of the Carlos III Health Institute, Madrid, Spain. 3. Unitat d'Al.lergia, Servei de Neumologia i Al.lergia Respiratoria, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Spanish Research Network on Adverse Reactions to Allergens and Drugs (RIRAAF: Red de Investigacion de Reacciones Adversas a Alergenos y Farmacos) of the Carlos III Health Institute, Madrid, Spain. 4. Unitat d'Al.lergia, Servei de Neumologia i Al.lergia Respiratoria, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 5. Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. 6. Office of Science and Technology and Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Md. 7. Laboratory of Molecular Immunogenetics, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Md.
Abstract
BACKGROUND: Lipid transfer protein (LTP), an abundant protein in fruits, vegetables, and nuts, is a common food allergen in Mediterranean areas causing diverse allergic reactions. Approximately 40% of food-related anaphylaxis induced by LTPs requires nonsteroidal anti-inflammatory drugs (NSAIDs) as a triggering cofactor. OBJECTIVE: We sought to better understand the determinants of NSAID-dependent and NSAID-independent LTP-induced anaphylaxis (LTP-A). METHODS: Selection of patients was based on a proved clinical history of NSAID-dependent or NSAID-independent anaphylaxis to LTPs, positive skin prick test response to LTPs, and serum LTP IgE. Whole-transcriptome (RNA sequencing) analysis of blood cells from 14 patients with NSAID-related LTP-A (NSAID-LTP-A), 7 patients with LTP-A, and 13 healthy control subjects was performed to identify distinct gene expression signatures. RESULTS: Expression of genes regulating gastrointestinal epithelial renewal was altered in both patient sets, particularly in those with LTP-A, who also presented with gene expression profiles characteristic of an inflammatory syndrome. These included altered B-cell pathways, increased neutrophil activation markers, and increased reactive oxygen species levels. Increased expression of the IgG receptor (CD64) in patients with LTP-A was mirrored by the presence of LTP-specific IgG1 and IgG3. Conversely, patients with NSAID-LTP-A were characterized by reduced expression of IFN-γ-regulated genes and IFN-γ levels, as well as upregulated expression of adenosine receptor 3 (ADORA3) and genes related to adenosine metabolism. CONCLUSIONS: Gene ontology analysis suggests disturbances in gut epithelial homeostasis in both groups with LTP-A, with potential integrity breaches in patients with LTP-A that might explain their distinct inflammatory signatures. Differential regulation in patients with LTP-A and those with NSAID-LTP-A of the IFN-γ pathway, IgG receptors, and ADORA3 might provide the pathogenic basis of their distinct responses. Published by Elsevier Inc.
BACKGROUND:Lipid transfer protein (LTP), an abundant protein in fruits, vegetables, and nuts, is a common food allergen in Mediterranean areas causing diverse allergic reactions. Approximately 40% of food-related anaphylaxis induced by LTPs requires nonsteroidal anti-inflammatory drugs (NSAIDs) as a triggering cofactor. OBJECTIVE: We sought to better understand the determinants of NSAID-dependent and NSAID-independent LTP-induced anaphylaxis (LTP-A). METHODS: Selection of patients was based on a proved clinical history of NSAID-dependent or NSAID-independent anaphylaxis to LTPs, positive skin prick test response to LTPs, and serum LTP IgE. Whole-transcriptome (RNA sequencing) analysis of blood cells from 14 patients with NSAID-related LTP-A (NSAID-LTP-A), 7 patients with LTP-A, and 13 healthy control subjects was performed to identify distinct gene expression signatures. RESULTS: Expression of genes regulating gastrointestinal epithelial renewal was altered in both patient sets, particularly in those with LTP-A, who also presented with gene expression profiles characteristic of an inflammatory syndrome. These included altered B-cell pathways, increased neutrophil activation markers, and increased reactive oxygen species levels. Increased expression of the IgG receptor (CD64) in patients with LTP-A was mirrored by the presence of LTP-specific IgG1 and IgG3. Conversely, patients with NSAID-LTP-A were characterized by reduced expression of IFN-γ-regulated genes and IFN-γ levels, as well as upregulated expression of adenosine receptor 3 (ADORA3) and genes related to adenosine metabolism. CONCLUSIONS: Gene ontology analysis suggests disturbances in gut epithelial homeostasis in both groups with LTP-A, with potential integrity breaches in patients with LTP-A that might explain their distinct inflammatory signatures. Differential regulation in patients with LTP-A and those with NSAID-LTP-A of the IFN-γ pathway, IgG receptors, and ADORA3 might provide the pathogenic basis of their distinct responses. Published by Elsevier Inc.
Entities:
Keywords:
Anaphylaxis; food allergy; lipid transfer protein syndrome; nonsteroidal anti-inflammatory drugs; transcriptome analysis
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