the IL1RL1 gene ST2 is a member of the toll-like/interleukin-1 receptor superfamily that exists in both membrane-bound (ST2 ligand) and soluble circulating forms (sST2). The cytokine interleukin-33 (IL-33) is the ligand for this receptor and soluble ST2 levels reflect IL-33 dependent cardioprotective signaling. ST2 is selectively expressed on T helper type 2 cells (TH2), regulatory T cells (Treg), mast cells, and cardiomyocytes. Soluble ST2 (sST2) sequesters IL-33, does not signal, and functions as a decoy receptor. ST2 is now well-recognized as a diagnostic and prognostic biomarker of cardiac stress in acute heart failure. Elevated ST2 levels indicate severe adverse cardiac remodeling and tissue fibrosis in response to myocardial infarction, acute coronary syndrome, or worsening heart failure. ST2 responses are independent of other cardiac biomarkers such as highly sensitive troponin, GDF-15, BNP, NT-proBNP, and galectin-3. ST2 is a mediator of inflammation in several diseases including asthma, rheumatoid arthritis, pulmonary fibrosis, inflammatory bowel disease (IBD), graft-versus-host disease (GVHD) and collagen disease. The reference range for sST2 is significantly higher in normal men (8.6–49.3 ng/mL) than women (7.2–33.5 ng/mL).
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