Soluble ST2 is a marker for acute cardiac allograft rejection

Ann Thorac Surg. 2011 Dec;92(6):2118-24. doi: 10.1016/j.athoracsur.2011.07.048. Epub 2011 Oct 28.


Background: Soluble ST2 (sST2), an interleukin (IL)-1 receptor family member, has a role in immunologic tolerance and has also emerged as a biomarker of cardiac stretch and remodeling. The sST2 role in heart transplantation is still unknown.

Methods: From the heart transplantation population at our institution (n = 74), we selected a subset of 26 patients who had an acute rejection episode in the first year after transplantation (35%; 52 ± 14 years; 76% men). Endomyocardial biopsy (EMB) results obtained at the time of the first rejection episode represented the rejection cohort (n = 26). Each patient served as a control to himself or herself, with EMB without rejection obtained before and after the rejection episode (n = 52). All laboratory measurements and blood samples were obtained at the time of EMB.

Results: sST2 concentrations rose significantly in the context of acute rejection (130 [60 to 238] versus 51 ng/mL [28 to 80]; p = 0.002). Tertile analyses of sST2 concentrations revealed a graded association with rejection (p = 0.002) and repeated measurement analyses showed that sST2 concentrations were significantly modulated by the presence of rejection (p = 0.001). In receiver operator characteristic (ROC) analysis, sST2 had an area under the curve (AUC) of 0.72; the optimal cutoff point was 68 ng/mL (positive predictive value of 53%, negative predictive value of 83%), which predicted acute cellular rejection (odds ratio [OR] 4.9; 95% confidence interval [CI], 1.7 to 14.5; p = 0.004). The addition of sST2 values to those for the N-terminal pro B-type natriuretic peptide (NT-proBNP) resulted in a significant improvement on the integrated discrimination index (IDI) for rejection (relative improvement of 24%; p = 0.021).

Conclusions: sST2 concentrations are modulated by the presence of acute rejection and provide complementary predictive ability to NT-proBNP for the biochemical identification of rejection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Biomarkers
  • Biopsy
  • Cross-Sectional Studies
  • Female
  • Graft Rejection*
  • Heart Transplantation / adverse effects*
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Male
  • Middle Aged
  • Myocardium / pathology
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Predictive Value of Tests
  • ROC Curve
  • Receptors, Cell Surface / blood*
  • Receptors, Cell Surface / physiology
  • Transplantation, Homologous


  • Biomarkers
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Peptide Fragments
  • Receptors, Cell Surface
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain