Soluble ST2 Is a Marker for Acute Cardiac Allograft Rejection

• Published in: The Annals of thoracic surgery Vol. 92; no. 6; pp. 2118 - 2124
• Main Authors: Pascual-Figal, Domingo A., MD, PhD, Garrido, Iris P., MD, Blanco, Rosa, MD, Minguela, Alfredo, PhD, Lax, Antonio, PhD, Ordoñez-Llanos, Jordi, PhD, Bayes-Genis, Antoni, MD, PhD, Valdés, Mariano, MD, PhD, Moore, Stephanie A., MD, Januzzi, James L., MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2011; Elsevier
• Subjects: Acute Disease; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Biomarkers; Biopsy; Cardiology. Vascular system; Cardiothoracic Surgery; Cross-Sectional Studies; Female; Graft Rejection; Heart Transplantation - adverse effects; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Medical sciences; Middle Aged; Myocardium - pathology; Natriuretic Peptide, Brain - blood; Peptide Fragments - blood; Pneumology; Predictive Value of Tests; Receptors, Cell Surface - blood; Receptors, Cell Surface - physiology; ROC Curve; Surgery; Transplantation, Homologous; 34; N-terminal pro B-type natriuretic peptide; orthotopic heart transplantation; ROC; LVEF; IQR; interquartile range; sST2; left ventricular ejection fraction; NT-proBNP; endomyocardial biopsy; OHT; EMB; receiver operating characteristic; soluble form of ST2; Heart; Graft(material); Acute; Biological marker; Transplantation; Homotransplantation; Rejection; Treatment; Surgery; Graft; Anesthesia; Circulatory system; Cardiology
• ISSN: 0003-4975; 1552-6259
• DOI: 10.1016/j.athoracsur.2011.07.048

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.