Biomarkers in renal transplantation: An updated review

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.