Table 4.
Selected promising molecules and pathways evaluated as biomarkers in acute rejection[7]
| Biomarker | Sample (assay method) | Patients/samples | Rejection/no rejection | Sensitivity/specificity (%) | PPV/NPV(%) | AUC |
| Granzyme B, perforin and FasL[74] | PBL (PCR) | 25/31 | 11/20 | 100/95 | 100/95 | NA |
| FOXP3[88] | PBL, urine (PCR) | 65/78 | 20/58 | 94-100/ 95/100 | 94-100/ 95/100 | 0.95-1.00 |
| Granzyme B, perforin[75] | Urine (PCR) | 85/151 | 24/127 | 79-83/77-83 | NA | NA |
| OX40, OX40L, PD-1 and FOXP3[76] | Urine (PCR) | 46/46 | 21/25 | 95/92 | NA | 0.98 |
| CD3ε,CXCL10, 18S rRNA[77] | Urine (PCR) | 485/4300 | 43/1,70 | 79/78 (71/72) | NA | 0.85 (0.74) |
| TIM-3[81] | PBL, urine (PCR) | 115/160 | 65/95 | 87-100/95-100 | 87-100/93-100 | 0.96-1.00 |
| CXCL9, CXCL10[78] | Urine (multiplex bead assay) | 156/156 | 25/131 | 80-86/76-80 | NA | 0.83-0.87 |
| CXCL9 mRNA and protein[79] | PBL, urine (PCR, ELISA, SELDI-TOF-MS | 280/2770 | 37/113 | 66.7-85.2/ 79.6/80.7 | 61.5/67.6/83-92 | 0.78-0.85 |
| miR-142-5p | Biopsy sample (PCR) | 32/33 | 12/21 | 92-100/90-95 | NA | 0.96-0.99 |
| miR-155 | ||||||
| miR-223[83] | ||||||
| miR-210[85] | Urine (PCR) | 81/88 | 68/20 | 52/74 | NA | 0.7 |
| IFNγ-producing memory T cells[89] | PBL (ELISPOT) | 23/23 | 12/10 | 80/83 | NA | 0.8 |
All the studies include a validation set. PPV: Positive predictive value; NPV: Negative predictive value; AUC: Area under the curve; PBL: Peripheral blood lymphocytes; PCR: Polymerase chain reaction; NA: Not available; PD-1: Programmed death 1; CXCL10: Interferon-inducible cytokine IP-10; 18S rRNA: 18S ribosomal RNA; TIM-3: T-cell immunoglobulin and mucin-domain containing-3; CXCL9: C-X-C motif chemokine 9; ELISA: Enzyme-linked immunosorbent assay; SELDI-TOF-MS: Surface-enhanced laser desorption/ionization time-of-flight MS; miRNA: microRNA; IFNγ: Interferon gamma; ELISPOT: Enzyme-linked immunoSpot.