Expression of STAT3, IL27p28 and IL12p35 is deregulated and linked to autoimmune markers in chronic spontaneous urticaria

Background Chronic spontaneous urticaria (CSU) is a common inflammatory disorder characterized by weals, angio-oedema, 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, IL27p28 (IL30) and IL12p35 (IL12A). Objectives To investigate patients with CSU and the expression of STAT3, STAT1, IL27p28 and IL12p35, and possible links to clinical features. Methods We enrolled 26 patients with CSU and 19 healthy controls (HCs) and determined their expression levels of STAT3, STAT1, IL27p28 and IL12p35 by quantitative real-time polymerase chain reaction. Patients were assessed for total IgE and IgG-anti-thyroid peroxidase (TPO), markers of autoimmune CSU. Results Patients with CSU showed significantly higher expression of STAT3 but not STAT1: 17 (65%) and 10 (38%) of the 26 had elevated STAT3 expression and STAT3/STAT1 ratios, respectively, as compared with only 1 (5%) of the 19 HCs. High STAT3 expression and STAT3/ STAT1 ratios were linked to low IgE and elevated IgG-anti-TPO. As compared with HCs, patients with CSU had markedly lower and correlated IL27p28 and IL12p35 mRNA expression levels. Low IL27p28 and IL12p35 expression levels were linked to higher STAT3/STAT1 ratios and low IgE. Conclusions STAT3 upregulation and higher STAT3/STAT1 ratios, along with IL27p28 and IL12p35 downregulation, clusters 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.