Lee, KH and Bosco, A and O'Sullivan, M and Song, Y and Metcalfe, J and Yu, K and Mullins, BJ and Loh, R and Zhang, G, Identifying gene network patterns and associated cellular immune responses in children with or without nut allergy, World Allergy Organization Journal, 15, (2) Article 100631. ISSN 1939-4551 (2022) [Refereed Article]
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© 2022 The Authors. Published by Elsevier Inc. on behalf of World Allergy Organization. This is an open access article under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Background: Although evidence suggests that the immune system plays a key role in the pathophysiology of nut allergy, the precise immunological mechanisms of nut allergy have not been systematically investigated. The aim of the present study was to identify gene network patterns and associated cellular immune responses in children with or without nut allergy.
Methods: Transcriptome profiling of whole blood cells was compared between children with and without nut allergy. Three genes were selected to be validated on a larger cohort of samples (n = 86) by reverse transcription-polymerase chain reactions (RT-qPCR). The composition of immune cells was inferred from the transcriptomic data using the CIBERSORTx algorithm. A co-expression network was constructed employing weighted gene co-expression network analysis (WGCNA) on the top 5000 most variable transcripts. The modules were interrogated with pathway analysis tools (InnateDB) and correlated with clinical phenotypes and cellular immune responses.
Results: Proportions of neutrophils were positively correlated and CD4+ T-cells and regulatory T-cells (Tregs) were negatively correlated with modules of nut allergy. We also identified 2 upregulated genes, namely Interferon Induced With Helicase C Domain 1 (IFIH1), DNA damage-regulated autophagy modulator 1 (DRAM1) and a downregulated gene Zinc Finger Protein 512B (ZNF512B) as hub genes for nut allergy. Further pathway analysis showed enrichment of type 1 interferon signalling in nut allergy.
Conclusions: Our findings suggest that upregulation of type 1 interferon signalling and neutrophil responses and downregulation of CD4+ T-cells and Tregs are features of the pathogenesis of nut allergy.
|Item Type:||Refereed Article|
|Keywords:||biomarker, food allergy, nut allergy, RNA sequencing, RT-qPCR, WGCNA, transcriptome, bioinformatics|
|Research Division:||Biological Sciences|
|Research Group:||Bioinformatics and computational biology|
|Research Field:||Biological network analysis|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Song, Y (Dr Yong Song)|
|Deposited By:||Menzies Institute for Medical Research|
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