Table 2.
Significant publications evaluating donor-derived cell-free DNA and microRNA in the evaluation of heart transplant rejection.
| Publication | Study name | Patient population & study design | Description | Outcome |
|---|---|---|---|---|
| dd-cfDNA | ||||
| Khush et al. (9) | D-OAR | 740 recipients ≥15 y, multicenter, prospective | Derivation and validation of clinically available (Allosure®) assay with 405 SNPs | dd-cfDNA threshold of 0.2% with 12% PPV and 97% NPV to detect ACR ≥ 2R or pAMR ≥ 1 |
| Richmond et al. (50) | DTRT | 101 children, 73 adults, multicenter, prospective | 94 SNP dd-cfDNA assay (no longer clinically available) | dd-cfDNA threshold of 0.3% with 85% PPV and 82% NPV to detect ACR ≥ 1R or pAMR ≥ 1 |
| Agbor-Enoh et al. (5) | GRAfT | 171 adults, multicenter, prospective | Whole genome, shotgun sequencing (>1 million SNPs) | dd-cfDNA threshold of 0.25% with 20% PPV and 99% NPV; distinct prediction of ACR and AMR |
| Kim et al. (51) | 223 adults, cross-sectional | Clinically available (ProsperaTM) dd-cfDNA assay with evaluation of >13,000 SNPs | dd-cfDNA threshold of 0.15% with 25% PPV and 97% NPV to detect ACR ≥ 2R or pAMR ≥ 1 | |
| MicroRNA | ||||
| Duong Van Huyen et al. (42) | 4 French centers, 113 patients, Case-control study | Pre-selected evaluation of 14 miR transcripts by RT-PCR, from both EMB and serum samples | Four miRs were differentially expressed in tissue and serum and validated in ACR and AMR as compared to controls | |
| Dewi et al. (52) | 6 Canadian centers, 63 patients, Case-control study | Pre-selected miRs evaluated by RT-PCR evaluation in serum | Two miRs were associated with ACR, after controlling for immunosuppressive drug levels, kidney function, and C-reactive protein | |
| Constanso-Conde et al. (53) | 1 Spanish center, 66 patients, Prospective Cohort study | Pre-selected evaluation of differential miR expression in ACR by RT-PCR | miR-181a-5p was differentially expressed in ACR ≥ 2R with rise and fall pattern associated with development/treatment of rejection | |
| Shah et al. (43) | GRAfT | 5 U.S. centers, 157 patients, Case-control study | Next generation sequencing evaluation of miR expression | Distinct miR scores between 0 and 100 were able to identify and distinguish ACR (32% PPV and 98% NPV) and AMR (37% PPV and 97% NPV |
ACR, acute cellular rejection; dd-cfDNA, donor-derived cell-free DNA; miR, microRNA; pAMR, pathologic antibody-mediated rejection; NPV, negative predictive value; SNPs, single nucleotide polymorphisms.