Soluble ST2: A complex and diverse role in several diseases.

The Suppression of Tumorigenicity 2 protein (ST2) is a member of the interleukin (IL) 1 receptor family with transmembrane (ST2L) and soluble (sST2) isoforms that are (over)expressed in several cells in different conditions and following various triggers (e.g. inflammation, stress). The ligand of ST2 is IL-33, which on binding to ST2L results in nuclear signalling and immunomodulatory action in various cells (tumour, immune, heart). sST2, that is released in the circulation, functions as a »decoy« receptor of IL-33 and inhibits IL-33/ST2L signalling and beneficial effects. The importance and role of the ST2/IL-33 axis and sST2 have been evaluated and confirmed in several inflammatory, cancer and cardiac diseases. sST2 is involved in homeostasis/pathogenesis of these diseases, as the counterbalance/response on IL-33/ST2L axis activation, which is triggered and expressed during developing fibrosis, tissue damage/inflammation and remodelling. In clinical studies, sST2 has been recognised as an important prognostic marker in patients with cardiac disease, including patients with chronic kidney disease where specific characteristics of sST2 enable better assessment of the risk of End-Stage Renal Disease patients on dialysis. sST2 is also recognised as an important marker for monitoring treatment in heart failure patients. However, accurate measurement and interpretation of ST2 concentration in serum/plasma samples for routine and research applications require the use of appropriate methods and recognition of essential characteristics of both the methods and the analyte that may influence the result. sST2, as one of the most promising disease biomarkers, is deserving of further study and wider application in clinical practice.