Small nucleolar RNA networks are up‐regulated during human anaphylaxis

Abstract

Background Anaphylaxis is a severe, potentially life‐threatening allergic reaction driven primarily by the activation of mast cells. We still fail to understand factors underlying reaction severity. Furthermore, there is currently no reliable diagnostic test to confirm anaphylaxis in the emergency department (ED). Objective This study sought to explore gene expression changes associated with anaphylaxis severity in peripheral blood leucocytes and evaluate biomarker potential. Methods Microarray analysis (total RNA) was performed using peripheral blood samples from ED patients with moderate (n = 6) or severe (n = 12) anaphylaxis and sepsis (n = 20) at presentation (T0) and one hour later (T1). Results were compared between groups and healthy controls (n = 10 and n = 11 matched to anaphylaxis and sepsis patients, respectively). Changes in gene expression were determined using R programming language, and pathway analysis applied to explore biological processes and pathways associated with genes. Differentially expressed genes were validated in an independent cohort of anaphylaxis (n = 30) and sepsis (n = 20) patients, and healthy controls (n = 10), using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). Results Significant up‐regulation of small nucleolar RNAs (snoRNAs) was demonstrated in anaphylaxis compared to sepsis patients in the microarray cohort, at T0 and T1. qRT‐PCR analysis of the validation cohort showed five genes: SNORD61, SNORD8, SNORD69, SNORD119 and HIST1H1D to be significantly up‐regulated (adjusted p < 0.05) in severe anaphylaxis compared to sepsis. Seven genes (SNORD61, SNORD8, SCARNA21, SNORD69, SNORD110, SNORD119 and SNORD59A) were significantly up‐regulated (adjusted p < 0.05) in severe anaphylaxis compared to healthy controls. Conclusion This study demonstrates for the first time the unique involvement of snoRNAs in the pathogenesis of anaphylaxis and suggests they are not a general feature of systemic inflammation. Further investigation of snoRNA expression in anaphylaxis could provide insights into disease pathogenesis. Clinical relevance SnoRNAs are up‐regulated during acute anaphylaxis in humans and could potentially be used as biomarkers of severe anaphylaxis.

Genes involved in platelet aggregation and activation are downregulated during acute anaphylaxis in humans

“…We therefore propose that platelet activation is initiated early during the anaphylactic reaction, followed by rapid downregulation of aggregation receptors to mitigate the response. Interestingly, our work has previously shown the pathway of, ‘cellular response to platelet derived growth factor stimulus’ was upregulated during severe anaphylaxis at ED arrival, further supporting this theory 19 . Adrenaline is known to promote platelet activation and aggregation, and downregulation of platelet aggregation was not observed in patients who received adrenaline before ED arrival.…”

“…Previous analysis on gene set GSE69063 identified significantly dysregulated genes in anaphylaxis patients compared with healthy controls and sepsis patients. Upregulation of a small subset of snoRNAs was validated in an independent cohort 19 . The focus of this paper was to further interrogate this data set and make additional comparisons with trauma patients as an example of noninfectious inflammation in the ED.…”

“…50 Severe anaphylaxis was classified by presentation with cardiovascular symptoms including hypotension, cyanosis, loss of consciousness and collapse. 19 raw gene expression profile was downloaded from the public functional genomics data repository: Gene Expression Omnibus (GEO). This data set was generated using the Affymetrix Human Gene 2.1 ST Array.…”

“…We have previously interrogated a gene expression data set on anaphylaxis and sepsis, with the aim of identifying dysregulated genes and evaluating biomarker potential 19 . We reported the upregulation of small nucleolar RNA (snoRNA) networks during acute anaphylaxis, but not sepsis, and highlighted their potential to act as biomarkers 19 .…”

“…We have previously interrogated a gene expression data set on anaphylaxis and sepsis, with the aim of identifying dysregulated genes and evaluating biomarker potential 19 . We reported the upregulation of small nucleolar RNA (snoRNA) networks during acute anaphylaxis, but not sepsis, and highlighted their potential to act as biomarkers 19 . In the present analysis, we aim to further explore mechanisms driving anaphylaxis, and make additional comparisons with a cohort of trauma patients as an example of noninfectious inflammation in the ED.…”