Expression of STAT3, IL-27p28, and IL-12p35 Is Deregulated and Linked to Autoimmune Markers in Chronic Spontaneous Urticaria

Abstract

Abstract Background Chronic spontaneous urticaria (CSU) is a common inflammatory disorder characterized by wheals, angioedema, or both, for more than 6 weeks. Autoimmunity is held to be one of the most frequent causes, but little is known about the expression and relevance of autoimmunity-driving genes in CSU, such as STAT3, STAT1, IL-27p28, and IL-12p35. Objective To investigate CSU patients or the expression of STAT3, STAT1, IL-27p28, and IL-12p35 and possible links to clinical features. Methods Gene expression levels, in 26 CSU patients and 19 healthy controls (HCs), were determined by quantitative real-time PCR. CSU patients were assessed for total IgE and IgG-anti-TPO, markers of autoimmune CSU. Results Patients with CSU showed significantly higher expression of STAT3, but not STAT1, and 17 and 10 of 26 CSU patients had elevated STAT3 expression and STAT3/STAT1 ratios, respectively, as compared to only 1 of 19 HCs. High STAT3 expression and STAT3/STAT1 ratios were linked to low IgE and elevated IgG-anti-TPO. As compared to HCs, CSU patients had markedly lower and correlated IL-27p28 and IL-12p35 mRNA expression levels. Low IL-27p28 and IL-12p35 expression levels were linked to higher STAT3/STAT1 ratios and low IgE. Conclusion STAT3 upregulation, higher STAT3/STAT1 ratios, and IL-27p28 and IL-12p35 downregulation cluster with features of autoimmune CSU. The role of STAT3 as a potential pathogenic driver of autoimmune CSU and target of treatment should be explored further.