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Table 1 Laboratory-based biomarkers

From: Biomarkers in solid organ transplantation: establishing personalized transplantation medicine

 

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]

  1. 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.