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.