DOI: 10.1101/473561Nov 19, 2018Paper

Rewiring of Th-memory-associated gene co-expression networks underlie immunotherapy-induced changes in symptom expression in mite-sensitised atopics

BioRxiv : the Preprint Server for Biology
Anya C JonesPatrick G Holt


Background: Multiple regulatory mechanisms have been identified employing conventional hypothesis-driven approaches as contributing to allergen-specific immunotherapy outcomes, but understanding of how these integrate to maintain immunological homeostasis is incomplete. Objective: To explore the potential for unbiased systems-level gene co-expression network analysis to advance understanding of immunotherapy mechanisms. Methods: We profiled genome-wide allergen-specific Th-memory responses prospectively across 24mths of subcutaneous immunotherapy (SCIT) in 25 rhinitics, documenting changes in immunoinflammatory pathways and associated co-expression networks and their relationships to symptom scores to 36mths. Results: Prior to immunotherapy, mite-specific Th-memory response networks involved multiple discrete co-expression modules including those related to Th2-, Type1-IFN-, Inflammation-, and FOXP3/IL2-associated signalling. A signature comprising 109 genes correlated with symptom scores, and these mapped to cytokine signalling/T-cell activation-associated pathways, with upstream drivers including hallmark Th1/Th2- and inflammation-associated genes. Reanalysis after 3.5mths SCIT updosing detected minimal changes to pathway/ups...Continue Reading

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Gene Expression
Up-Regulation (Physiology)

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