Methods: We collected peripheral blood mononuclear cells (PBMC’s) from 21 patients with active CIU disease and 10 non-atopic healthy controls. RNA was extracted from PBMC’s and prepared for Affymetrix GeneChip® Human Gene U133 plus 2.0 Array hybridization. The raw data were normalized and the gene expression of CIU patients was compared to that of normal controls.
Results: We found 149 genes that predicted CIU from normal controls (FDR<5%). The genes in the predictor are differentially expressed (P<0.001) with a minimum 2-fold difference between CIU patients and controls. The predictor was 100% successful in distinguishing patients with CIU from controls, and tested using leave one out cross-validation. Additionally we found that the upregulated genes seen in CIU most strongly correlated with monocytes, identified as cells expressing CD14 cell surface marker (p<0.001, r >0.8). Gene set enrichment analysis of CIU patients further revealed activation of a specific arm of the MAP-Kinase pathway utilized by monocytes (p<0.001, r >0.8).
Conclusions: Gene expression profiling can reliably distinguish patients with CIU from healthy controls. Our study findings suggest potential underlying mechanisms of CIU. These findings may provide guidance in developing biomarkers that would help determine subsets of patients who would be more likely to respond to variety of treatment options available.