Abstract
BACKGROUND: The pathophysiology of chronic idiopathic (spontaneous) urticaria (CIU) is poorly understood. OBJECTIVE: We hypothesized that a study of gene expression in active lesions from patients with CIU would uncover unexpected associations. METHODS: We enrolled eight patients with CIU and six healthy controls, and obtained 4 mm punch biopsy specimens of active lesions and unaffected skin of patients with CIU and of skin from normal controls. Routine histologic evaluation was performed, RNA was isolated, and gene expression data were assessed. Due to technical reasons, the final evaluation included six samples of lesional skin, six samples of nonlesional skin, and five samples of normal skin. RESULTS: As expected, lesional skin had more inflammatory cells per high-powered field (mean ± SE, 96 ± 6) than did samples from nonlesional skin of the subjects with CIU (17 ± 2) (p < 0.01). Lesions of CIU showed significant upregulation of 506 genes and reduced expression of 51 genes. Those most upregulated were predominantly involved in cell adhesion (e.g., selectin E [SELE]), cell activation (e.g., CD69), and chemotaxis (e.g., CCL2). Twelve independent canonical pathways with p ≤ 0.001 were identified (including intracellular kinase pathways (RAs-related nuclear protein [RAN] and Janus activated kinase/interferon), cytokine signaling pathways (IL-9, IL10, and IFN), a strong inflammatory response (interferon, IL-9, IL-10, inducible nitric oxide synthase and glucocorticoid pathways) and increased cell proliferation (RAN signaling, cell cycle control, and tRNA charging). CONCLUSIONS: This preliminary study describes a method to study gene activation in urticarial lesions and demonstrated a strong inflammatory response with a large variety of activated genes that are distinct from those reported with other dermatologic conditions.