Table 1.
Laboratory-based biomarkers
| Organ | Sample | Proposed mechanism | Biomarker | References | |
|---|---|---|---|---|---|
| (a) Pre-transplantation biomarkers | |||||
| Kidney, lung, liver | Blood (DNA) | Genetic variants in donor/recipient are associated with risk and severity of AR and with allograft survival | 15 SNPs, TLR, C3 | [39-44,46] | |
| Kidney | Biopsy (mRNA) | Expression profiles of innate immunity-related genes predict allograft survival | C3 | [47] | |
| Kidney | Serum (protein); biopsy (mRNA) | Novel immunogenic epitopes | Non-HLA antigens | [12,48-50] | |
| (b) Post-transplantation biomarkers: acute allograft rejection | |||||
| Kidney | Blood (PBMCs, mRNA), urine (mRNA) | Cytotoxic proteins indicate AR | FasL, GranzymeB, Perforine | [27,54,57,58] | |
| Kidney, lung, liver, heart | Blood (PBMCs), serum, BALF, urine (mRNA, protein) | Donor/recipient cytokine expression predicts/detects AR | CXCR, CXCL10 CXCL9 | [59-63] | |
| Kidney | Biopsy, blood (PBMCs, mRNA) | Alterations in miRNA are associated with AR | miR-142-5p, miR-155, miR-223 | [64-67] | |
| Kidney | Biopsy | Biomarkers for antibody-mediated rejection (diagnostic/predictive) | CD38, endothelial cell genes | [70,71] | |
| Kidney | Biopsy, serum (protein) | Antibodies against novel non-HLA antigens (diagnostic/predictive) | AT1R-AA, MICA, Duffy, Kidd, Agrin | [50,72-75] | |
| Kidney, heart | Biopsy, serum (mRNA, protein) | Integrative proteogenomic biomarkers predict and diagnose AR across organs | Novel non-HLA antigen PECAM1 | [12,76] | |
| Post-transplantation biomarkers: chronic allograft damage | |||||
| Kidney | Blood (mRNA), biopsy (mRNA), urine (mRNA) | Predictive peripheral genes and proteins for mild/moderate chronic allograft damage and chronic antibody-mediated damage | TRIB1, CCL2 | [13,77,82] | |
| Kidney, heart | Blood (protein), biopsy (mRNA), urine (protein) | Early diagnostic peripheral and urinary gene expression for IF/TA and anti-fibrotic target | KIM-1, CTGF | [78,79,85,86] | |
| Post-transplantation biomarkers: graft accommodation | |||||
| Liver, kidney | Blood (PBMCs, mRNA) | Peripheral gene expression identifies transplant recipients for discontinuation of immunosuppression | (a) Three classifiers of 2,3 and 7 genes; (b) 33-gene panel; (c) 343 genes | [88,89] | |
| Kidney | Blood (mRNA) | B-lymphocyte-related gene signature of tolerance in transplant patient PBMCs | (a) B-cell signature (IGKV1D-13, IGKV4-1, IGLL1); (b) B-cell signature, ratio of FOXP3/α-1,2-mannosidase |
[90,91] | |
AT1R-AA, agonistic antibodies against angiotensin type II receptor 1; BALF, bronchoalveolar fluid; CCL, CC chemokine ligand; FasL, Fas ligand; FOXP3, Forkhead box P3; IGKV, immunoglobulin kappa variable group; IGLL1, immunoglobulin lambda-like polypeptide 1; KIM-1, kidney injury molecule 1; TLR, Toll-like receptor; IF/TA, interstitial fibrosis/tubular atrophy.