Dysregulation of complement system and CD4+T cell activation pathways implicated in allergic response

Alves, Alexessander Couto, Bruhn, Soren, Ramasamy, Adaikalavan, Wang, Hui, Holloway, John W., Hartikainen, Anna-Liisa, Jarvelin, Marjo-Riitta, Benson, Mikael, Balding, David J. and Coin, Lachlan J. M. (2013) Dysregulation of complement system and CD4+T cell activation pathways implicated in allergic response. PLoS One, 8 10: e74821.1-e74821.15. doi:10.1371/journal.pone.0074821

Author Alves, Alexessander Couto
Bruhn, Soren
Ramasamy, Adaikalavan
Wang, Hui
Holloway, John W.
Hartikainen, Anna-Liisa
Jarvelin, Marjo-Riitta
Benson, Mikael
Balding, David J.
Coin, Lachlan J. M.
Title Dysregulation of complement system and CD4+T cell activation pathways implicated in allergic response
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-10
Sub-type Article (original research)
DOI 10.1371/journal.pone.0074821
Open Access Status DOI
Volume 8
Issue 10
Start page e74821.1
End page e74821.15
Total pages 15
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2014
Language eng
Abstract Allergy is a complex disease that is likely to involve dysregulated CD4+ T cell activation. Here we propose a novel methodology to gain insight into how coordinated behaviour emerges between disease-dysregulated pathways in response to pathophysiological stimuli. Using peripheral blood mononuclear cells of allergic rhinitis patients and controls cultured with and without pollen allergens, we integrate CD4+ T cell gene expression from microarray data and genetic markers of allergic sensitisation from GWAS data at the pathway level using enrichment analysis; implicating the complement system in both cellular and systemic response to pollen allergens. We delineate a novel disease network linking T cell activation to the complement system that is significantly enriched for genes exhibiting correlated gene expression and protein-protein interactions, suggesting a tight biological coordination that is dysregulated in the disease state in response to pollen allergen but not to diluent. This novel disease network has high predictive power for the gene and protein expression of the Th2 cytokine profile (IL-4, IL-5, IL-10, IL-13) and of the Th2 master regulator (GATA3), suggesting its involvement in the early stages of CD4+ T cell differentiation. Dissection of the complement system gene expression identifies 7 genes specifically associated with atopic response to pollen, including C1QR1, CFD, CFP, ITGB2, ITGAX and confirms the role of C3AR1 and C5AR1. Two of these genes (ITGB2 and C3AR1) are also implicated in the network linking complement system to T cell activation, which comprises 6 differentially expressed genes. C3AR1 is also significantly associated with allergic sensitisation in GWAS data.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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