Soluble ST2 is a marker for acute cardiac allograft rejection.
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.
Cardiology Service, Virgen de la Arrixaca Hospital and Department of Medicine, University of Murcia, Murcia, Spain. dapascual@servicam.com
Domingo A
DA
Pascual-Figal
Iris P
IP
Garrido
Rosa
R
Blanco
Alfredo
A
Minguela
Antonio
A
Lax
Jordi
J
Ordoñez-Llanos
Antoni
A
Bayes-Genis
Mariano
M
Valdés
Stephanie A
SA
Moore
James L
JL
Januzzi
D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001706:Biopsy; D003430:Cross-Sectional Studies; D005260:Female; D006084:Graft Rejection; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000097:blood* / Q000502:physiology; D014184:Transplantation, Homologous
D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain