The use of circulating donor specific antibody to predict biopsy diagnosis of antibody-mediated rejection and to provide prognostic value after heart transplantation in children

Abstract

Background: Antibody-mediated rejection (AMR) is a significant cause of mortality after heart transplantation (HT). Although the presence of donor specific antibody (DSA) is a risk factor for developing AMR, serial DSA testing is not widely performed. We aimed to investigate the predictive values and prognostic implications of circulating DSA using endomyocardial biopsy as the gold standard for AMR diagnosis in pediatric recipients of HT.

Methods: We performed a retrospective study in pediatric recipients of HT followed during the period 2009-2013 with at least 1 biopsy paired with DSA testing. Positive DSA was defined at mean fluorescent intensity (MFI) ≥2,000 using single antigen bead testing. Statistical analyses included 2 × 2 contingency tables, receiver operating characteristic analysis for optimal MFI cutoffs, Spearman correlation of MFI strength to AMR grade, and Kaplan-Meier analysis of event-free survival.

Results: Of 66 children included, 27 (41%) had ≥1 DSA positive test. DSA testing had a sensitivity of 92.6%, specificity of 62.2%, positive predictive value of 24.0%, and negative predictive value of 98.5% for biopsy diagnosis of AMR at our institution. There was a statistically significant correlation between higher MFI and higher AMR grade. Patients with positive DSA and AMR had similar survival early after DSA detection but trended toward lower cardiovascular event-free survival later compared with patients without DSA and a negative biopsy.

Conclusions: The results of DSA testing in this cohort showed excellent sensitivity and negative predictive value for biopsy-diagnosed AMR, suggesting that DSA testing may aid in the non-invasive prediction of AMR absence in HT. The correlation of DSA MFI strength with higher AMR biopsy grade and the trend toward differences in longer term cardiovascular outcomes provide evidence for routine DSA monitoring after pediatric HT.

Keywords: antibody-mediated rejection; donor specific antibody; endomyocardial biopsy; heart transplantation; pediatrics.