I. Billiar1, J. Guardado1, J. Brown1, O. Abdul-Malak1, Y. Vodovotz1, T. R. Billiar1, R. A. Namas1 1University Of Pittsburgh,Pittsburgh, PA, USA
Introduction: Soluble suppression of tumorigenicity 2 (sST2), a decoy receptor for interleukin (IL)-33, has emerged as a novel biomarker in various disease processes. Recent studies have elucidated on the role of IL-33/sST2 complex in modulating the balance of Th1/Th2 immune response following tissue stress. However, the role of sST2 as a biomarker following traumatic injury remains unclear. To address this, we sought to evaluate serum sST2 correlations with in-hospital outcomes and mortality as endpoints in blunt trauma patients.
Methods: We retrospectively analyzed clinical and biobank data of 493 blunt trauma victims (472 survivors [mean age: 48±0.9; injury severity score (ISS): 20±0.5] and 19 non-survivors [mean age: 59±4.5; ISS: 23±2]) admitted to the intensive care unit (ICU). Given the confounding impact of age on the inflammatory response, we derived a matched survivor sub-group (n=19; mean age: 60±3; ISS: 23±2) using an IBM SPSS® case-control matching algorithm. Serial blood samples were obtained from all patients (3 samples within the first 24 h and then from day (D) 1 to D7 post-injury). Thirty inflammatory biomarkers were assayed using Luminex™. Two-Way Analysis of Variance was used to compare groups (P<0.05). Spearman rank correlation was performed to determine the association of circulating sST2 levels with in-hospital outcomes and biomarker levels.
Results: Circulating sST2 levels of the non-survivor cohort were statistically significantly elevated at 12 h post-injury and remained elevated up to D7 when compared to the parent survivor cohort. Admission sST2 levels obtained from the first blood draw within 12 h post-injury in the parent survivor cohort correlated weakly but positively with admission base deficit (correlation coefficient [cc]=0.1; P=0.029), the shock index (heart rate/systolic blood pressure; cc=0.2; P=0.0006), creatinine (cc=0.1; P=0.02), INR (cc=0.1, P=0.03), ISS (cc=0.1, P=0.008), and the average Marshall multiple organ dysfunction score between D1 to D7 (cc=0.1, P=0.04). Analysis of biomarker correlations in the matched survivor group showed that sST2 correlates strongly and positively with the type 2 cytokines IL-4 (cc=0.6, P=0.002), IL-5 (cc=0.5; P=0.01), and IL-13 (cc=0.4, P=0.02), as well as IL-21 (cc=0.5; P=0.02), IL-2 (cc=0.5, P=0.02), sIL-2Rα (cc=0.5, P=0.02), and IL-17 (cc=0.5, P=0.03). Interestingly, the sST2 levels in the non-survivor group had negative correlations with MIG (cc= -0.6; P=0.02) and IL-10 (cc= -0.5; P=0.02) with no positive correlations with the other biomarkers.
Conclusion: Elevations in serum sST2 levels are associated with poor clinical trajectories and mortality following blunt trauma. The lack of positive correlations of sST2 with other mediators in non-survivors (unlike the survivors) suggests that the host response becomes dysregulated early in patients that go onto to die. Thus, sST2 could serve as an early prognostic biomarker in trauma patients.