Relationship of Noninvasive Detection of Allograft Rejection and Injury (Donor-Derived Cell Free DNA and Gene Expression Profiling) and Tissue-Based Molecular Microscopic Diagnosis After Heart Transplantation

Abstract

<h3>Purpose</h3> Non-invasive quantitative detection of allograft injury through donor-derived cell-free DNA (dd-cfDNA; AlloSure) and gene expression profile (GEP; AlloMap) are used for surveillance of antibody-mediated rejection (AMR) and cell-mediated rejection (CMR) in heart transplant (HTx) patients. While dd-cfDNA and GEP correlate well with the histologic assessment of endomyocardial biopsy (EMB), the relationship with molecular microscopic transcript (MMDx) remains unknown in HTx. <h3>Methods</h3> We retrospectively reviewed HTx patients from 2020-2021 who underwent dd-cfDNA, GEP and EMB with histology and MMDx results. The results were compared using non-parametric analyses with Kruskal-Wallis test. CMR ISHLT ≥ Grade 2R and AMR ≥1 from histology and MMDx were considered as rejection. <h3>Results</h3> A total of 108 patients were included in the analysis. Through MMDx, there were 9 patients with CMR, 39 with AMR, 2 with mixed rejection (AMR/CMR), and 58 with no rejection. Elevations in dd-cfDNA occurred in the CMR, AMR, mixed rejection groups, when compared to no rejection (Median: 0.24%, 1.20%, 2.90%, 0.12%, respectively, P<0.001). GEP was not different between different groups of MMDx. The AUC for dd-cfDNA and rejection by MMDx was 0.89 [95% C.I.: 0.83-0.96]. <h3>Conclusion</h3> The non-invasive quantitative detection of dd-cfDNA correlated well with the tissue molecular microscopic transcript in both AMR and CMR in heart transplant patients. Further study of how the addition of dd-cfDNA/GEP and MMDx would complement the diagnosis and prognosis of allograft injury in heart transplantation should be performed.