Document Type

Journal Article

Publication Title

World Allergy Organization Journal

Volume

15

Issue

2

Publisher

Elsevier

School

School of Science

Funders

Telethon-Perth Children’s Hospital Research Fund (TPCHRF) Australian Government Research Training Program (RTP) Stipend Scholarship.

Comments

Lee, K. H., Bosco, A., O'Sullivan, M., Song, Y., Metcalfe, J., Yu, K., ... & Zhang, G. (2022). Identifying gene network patterns and associated cellular immune responses in children with or without nut allergy. World Allergy Organization Journal, 15(2), 100631. https://doi.org/10.1016/j.waojou.2022.100631

Abstract

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.

DOI

10.1016/j.waojou.2022.100631

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Share

 
COinS