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 leukocytes 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 to 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 upregulation 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 upregulated (adjusted p<0.05) in severe anaphylaxis compared to sepsis. Seven genes (SNORD61, SNORD8, SCARNA21, SNORD69, SNORD110, SNORD119, and SNORD59A) were significantly upregulated (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 upregulated during acute anaphylaxis in humans, and could potentially be used as biomarkers of severe anaphylaxis.
|Pages (from-to)||1310 - 1321|
|Number of pages||12|
|Journal||Clinical & Experimental Allergy|
|Publication status||Published - Oct 2021|