Changes in Whole Blood Transcriptome During Peanut-Induced Anaphylaxis and Correlation with Symptoms

Food allergy is the commonest cause of anaphylaxis, but why IgE-mediated reactions cause anaphylaxis in some cases but not in others remains unknown. We applied whole blood transcriptomic analysis to blood samples obtained during double-blind, placebo-controlled food challenges (DBPCFC) to peanut, and analysed the resulting data by reaction severity. 37 adults and 57 children underwent DBPCFC. Anaphylaxis (NIAID criteria) occurred in 31 (84%) adults and 27 (47%) children, of whom 17 children and 17 adults experienced lower respiratory symptoms. 20 individuals with anaphylaxis underwent at least one further challenge, at which more mild (ie non-anaphylaxis) symptoms occurred. Significant changes in gene expression (predominantly related to innate immune activation) were seen at 2 hours following reaction (adj P<0.01) but not at time of objective reaction nor at baseline prior to challenge. This implies that acute reactions are likely due to the release of preformed mediators, rather than changes in gene expression. No significant differences were observed in transcriptome when comparing anaphylaxis reactions (skin/gut involvement only) with non-anaphylaxis. In contrast, anaphylaxis involving lower respiratory and/or laryngeal symptoms was associated with altered expression of 22 genes (adj P<0.05). This is the first study to assess the relationship between reaction severity and gene expression during acute IgE-mediated reactions in a large cohort of peanut-allergic individuals. Despite reactions involving skin and persistent gut symptoms being classified as anaphylaxis (according to NIAID criteria), such reactions had a similar profile to non-anaphylaxis reactions. This suggests a different underlying pathophysiology for anaphylaxis reactions also involving laryngeal and/or lower respiratory symptoms.