Transcriptome analysis of severely active chronic spontaneous urticaria shows an overall immunological skin involvement

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The knowledge about chronic spontaneous urticaria (CSU) phenotypes is based on its clinical characteristics, associated comorbidities, course of the disease, and its response to the available effective drugs. Genotype expression and its further correlation with CSU phenotypes are still unknown. We describe the cutaneous transcriptome of patients suffering a severely active CSU refractory to antihistamine treatment.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Through the bioinformatic analysis of the whole Human Genome with Oligo Microarrays and quantitative real‐time polymerase chain reaction (qPCR), relevant genes expressed in nonlesional (NLS‐CSU) and lesional skin (LS‐CSU) and peripheral blood were identified in 20 patients suffering from severely active CSU and 10 healthy controls (HCs).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>From 39 genes differentially expressed in NLS‐CSU when compared with HCs, 31 (79.48%) were confirmed by qPCR corresponding to genes involved in epidermal homeostasis and dermal repair. From the analysis comparing LS‐CSU with NLS‐CSU, a selection of 142 genes was studied with qPCR, and 103 (72.53%) were confirmed. Differentially expressed genes in the phenomenon of wheal development are involved in a variety of biological functions as, epidermal differentiation, intracellular signal function, transcriptional factors cell cycle differentiation, inflammation, or coagulation. Differentially expressed genes that uniformly increase or decrease along the skin worsening until the wheal appearance is shown.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The skin of CSU patients with a severely active disease shows an overall immunological skin involvement showing a peculiar gene profile.</jats:p></jats:sec>