Presented at:
2007 American Academy of Allergy, Asthma & Immunology Annual Meeting
San Diego, CA, February 23-27, 2007
Transcriptome Seasonal Regulation in Ragweed Allergy
Seyfert VL, Asare AL, Bourcier K, Wang R, Gao Z, Casale TB
Rationale: To examine the effects of treatment on gene expression in relation to seasonal effects, transcriptional regulation in ragweed allergy clinical trial participants treated with Omalizumab plus RIT (OM+IT), Omalizumab (OM) or RIT alone (PL+IT), and Placebo (PL+PL) was studied.
Methods: For 34 participants chosen from a single clinical trial site, peripheral blood RNA was collected at study weeks -9 (baseline), 0 (administration of RIT and 9-weeks post OM/PL), 1 (one week post RIT), 5 (early ragweed season), 9 (late ragweed season) and 13 (1 week post ragweed season). Robust Multiarray Average (RMA) normalized data was fit into linear models to identify differential expression > 1.5 fold from the prior visit using the Bioconductor/R package LIMMA. The Benjamini-Hochberg FDR correction was applied.
Results: Dramatic changes in gene expression were observed between pre- to mid- and mid- to post-ragweed season in all treatment groups (p<0.05). Many of these differentially regulated genes correspond to immune regulation/function pathways and include several key transduction molecules. ). Specifically, genes related to IL-10, IL-2, IL-4, and IL6 receptor pathways were most affected (p<0.05). Seasonal effect on immune function pathways was most pronounced in the PL+PL group. Interestingly, both severity score in individuals across all treatment groups and therapy influenced profiles of seasonally regulated genes.