Molecular Profiling Distinguishes Chronic Idiopathic Urticaria From Normal Volunteers And Reveals Novel Aspects Of Disease Biology

RATIONALE: Chronic Idiopathic Urticaria (CIU) is a disorder characterized by varying severity, duration and response to treatment. The pathogenesis is unknown, yet CIU affects many. We explored the hypothesis that gene expression profiles of mononuclear cells (MC) obtained from patients would demonstrate distinct differences compared to those obtained from controls. We reasoned that the molecular profile of patients with CIU would offer new clues regarding the biology of the disease and allow for the identification of novel markers and treatments of the disease. METHODS: 12 patients with CIU and 5 non-atopic controls were enrolled. MC were isolated from peripheral blood using Ficoll density centrifugation. MC were profiled for gene expression at the whole-genome level using Affymetrix U133plus DNA microarrays. The scanned data were normalized and the gene expression of CIU patients was compared to that of controls. We further analyzed the data for expression of genes associated with CD203c. RESULTS: We found 149 genes predicted CIU from controls. 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. Among these genes are regulators of cell trafficking, cell adhesion, homing and inflammation. We also found 125 genes that strongly correlated with the level of CD203c (r = >.75, p < 0.01). CONCLUSIONS: Gene expression profiling can reliably distinguish patients with CIU from controls. The enriched subset gene analysis suggests potential for novel mechanisms of disease, biomarker development and targeted treatment.