Molecular Profiling Distinguishes Patients With Active Idiopathic Anaphylaxis From Normal Volunteers And Reveals Novel Aspects Of Disease Biology

RATIONALE: Idiopathic anaphylaxis (IA) is a disorder characterized by episodes of anaphylaxis and spontaneous remission. There is heterogeneity within the disease with respect to severity, symptoms and response to treatment. We sought to investigate whether gene expression profiles of mononuclear cells (MC) obtained from IA patients demonstrate distinct differences compared to those obtained from controls. We reasoned that the molecular profile of patients with IA would reveal key elements of the biology of the disease and allow for the identification of novel markers and treatment. METHODS: 9 patients with IA 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 IA patients was compared to that of controls. We further analyzed the data for expression of genes associated with CD203c. RESULTS: We found 53 genes predicted IA from controls. The genes in the predictor are differentially expressed (P < 0.001) with a minimum 2-fold difference between IA patients and controls. The predictor was 100% successful in distinguishing patients with IA from controls, and tested using leave one out cross-validation. Among these genes are regulators of cell activation and mast cell/basophil degranulation. We also found 106 genes that strongly correlated with the level of CD203c (r = >.75, p < 0.01). CONCLUSIONS: Gene expression profiling can reliably distinguish patients with IA from controls. The gene analysis suggests potential for understanding mechanism of disease, biomarker development and targeted treatment.