Objective: Serum ST2, a member of the interleukin (IL) 1 receptor family, is a novel biomarker that reflects cardiac remodeling and fibrosis and is associated with poor prognosis in patients with heart failure (HF). The significance of ST2 levels after heart transplantation (HTx) is unknown.

Methods: Serum ST2 levels were measured 263 ± 346 days after HTx in 62 patients who underwent heart alone (50), heart-kidney (6) and heart-liver (6) transplant by an immunoassay. The cumulative effect of antibody mediated rejection (AMR) and cellular rejection (CR) was calculated by rejection scores, which was the sum of endomyocardial biopsy AMR or CR grading divided by number of biopsies during 3 years post-HTx. Patients were classified into normal or elevated (≥35 ng/ml) post-HTx ST2 level groups, then comparisons were made between groups using chi-quare tests, Wilcoxon rank sum tests, or Cox proportional hazards models to evaluate association between ST2 levels and cardiac allograft rejection, coronary allograft vasculopathy (CAV) and patient survival.

Results: Post-HTx ST2 levels were elevated in 31 (50%) patients. There were no significant differences in baseline characteristics between recipients with elevated and normal ST2 levels. ST2 levels did not correlate with other HF biomarkers [NT pro-BNP (658±559 ng/l) and Galectin 3 (19.8±7.4 ng/ml); p>0.05]. Mean follow up post-HTx was 81 ± 34 months. HTx recipients with elevated as compared to those with normal ST2 levels had significantly higher AMR score at 1, 2 and 3 years post-HTx (0.07 vs. 0.00; 0.07 vs. 0.01 and 0.06 vs. 0.01, respectively, p<0.05). There was no association between post-HTx elevated ST2 levels and CR, CAV and survival.

Conclusion: Elevated serum ST2 level is associated with increased risk for AMR after HTx. Our study for the first time implicates the role of ST2, an IL 1 receptor that binds to IL 33, in AMR.

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