IL-33/sST2 signaling pathway in pulmonary thromboembolism: A clinical observational study

Pulmonary thromboembolism (PTE) is a cardiovascular emergency that can result in mortality. In the interleukin-33 (IL-33) /soluble suppression of tumorigenicity 2 (sST2) signaling pathway, increased sST2 is a cardiovascular risk factor. This study aimed to investigate the effectiveness of biomarkers in the IL-33/sST2 signaling pathway in determining PTE diagnosis, clinical severity, and mortality.

This study was conducted as a single-center, prospective, observational study. Patients admitted to the emergency department and diagnosed with PTE constituted the patient group (n = 112), and healthy volunteers with similar sociodemographic characteristics constituted the control group (n = 62). Biomarkers in the IL-33/sST2 signaling pathway were evaluated for diagnosis, clinical severity, and prognosis.

IL-33 was lower in the patient group than in the control group (275.89 versus 403.35 pg/mL), while sST2 levels were higher in the patient group than in the control group (53.16 versus 11.78 ng/mL) (p < 0.001 and p = 0.001; respectively). The AUC of IL-33 to diagnose PTE was 0.656 (95 % CI: 0.580-0.726). The optimal IL-33 cut-off point to diagnose PTE was ≤304.11 pg/mL (56.2 % sensitivity, 79 % specificity). The AUC of sST2 to diagnose PTE was 0.818 (95 % CI: 0.752-0.872). The optimal sST2 cut-off point to diagnose PTE was >14.48 ng/mL (83 % sensitivity, 71 % specificity). IL-33 levels were lower in patients with mortality (169.85 versus 332.04 pg/mL) compared to patients without mortality, whereas sST2 levels were higher in patients with mortality (118.32 versus 28.07 ng/mL) compared to patients without mortality (p > 0.001 for both). The AUC of IL-33 to predict the mortality of PTE was 0.801 (95 % CI: 0.715-0.870). The optimal IL-33 cut-off point to predict the mortality of PTE was ≤212.05 pg/mL (75 % sensitivity, 79.5 % specificity). The AUC of sST2 to predict the mortality of PTE was 0.824 (95 % CI: 0.740-0.889). The optimal sST2 cut-off point to predict the mortality of PTE was >81 ng/mL (95.8 % sensitivity, 78.4 % specificity).

In the IL-33/ST2 signaling pathway, decreased IL-33 and increased sST2 are valuable biomarkers for diagnosis and prediction of mortality in patients with PTE.