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J Allergy Clin Immunol. 2016 Jan;137(1):137-146. doi: 10.1016/j.jaci.2015.05.042. Epub 2015 Jul 17.

Distinct transcriptome profiles differentiate nonsteroidal anti-inflammatory drug-dependent from nonsteroidal anti-inflammatory drug-independent food-induced anaphylaxis.

Author information

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.

KEYWORDS:

Anaphylaxis; food allergy; lipid transfer protein syndrome; nonsteroidal anti-inflammatory drugs; transcriptome analysis

PMID:
26194548
PMCID:
PMC4715677
DOI:
10.1016/j.jaci.2015.05.042
[Indexed for MEDLINE]
Free PMC Article

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