Transcriptome analysis reveals clues into the mechanisms of NSAID-dependent food anaphylaxis

Published Online: July 17, 2015

Food allergens are the major triggers for anaphylaxis, an acute and potentially life-threatening systemic allergic reaction. Often, induction of anaphylaxis in individuals presenting IgE antibodies (or “sensitive”) to the inciting allergens requires cofactors such as painkillers (aspirin, ibuprofen, etc) known as non-steroidal anti-inflammatory drugs (NSAID). However, the reasons for NSAID dependency in the manifestation of anaphylaxis in some individuals but not others are unknown.

In the article recently published in The Journal of Allergy & Clinical Immunology (JACI), Muñoz-Cano and colleagues use high-throughput sequencing to compare the gene expression patterns of patients with NSAID dependent to those with NSAID-independent food anaphylaxis. They collected blood samples of patients with documented NSAID-dependent or independent sensitivity to lipid transfer protein (LTP) variably present in fruits, vegetables, and nuts.

Gene expression analysis indicated constitutive defects in intestinal epithelium renewal in both groups, but more so in those with anaphylaxis without NSAID dependence. These defects were accompanied by increased gut permeability. The analysis also evidenced gene expression patterns characteristic of immunological diseases and neutrophil activation only in patients without the NSAID dependence, an observation the authors hypothesize may be linked to an intestinal barrier compromise. In addition, increased expression of the high affinity receptor for IgG antibodies (FcγRI) and elevated allergen-specific IgG1 and 3 levels in this, but not in NSAID-dependent anaphylaxis group, may also contribute to this anaphylaxis-prone phenotype. Unique patterns identified in patients with NSAID-dependent food anaphylaxis further included an increase in genes involved in nucleotide metabolism, a pathway promoted by NSAIDs, and a nucleoside receptor (ADORA3), which is known to potentiate mast cell responses to allergens.

This study thus presents convincing evidence for the existence of underlying patterns of gene expression, which predispose to the induction of food-induced anaphylaxis in the presence of co-factors such as NSAIDS. The report further suggests new and novel mechanisms that may underlie systemic reactions to antigens.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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