Role of novel biomarkers in kidney transplantation

Table 3 Summary of leukocyte subclass related biomarkers associated with immunologic outcomes

Ref.	n	Sample	Biomarkers	Outcome	Study conclusion
Luque et al[25], 2019	175	Plasma	donor reactive memory B cells (mBC)	ABMR	For-cause bx: mBC in 100% ABMR/DSA+ and most cABMR, +/- DSA [24/30 (80%) and 21/29 (72.4%)]. Protocol bx: mBC > dnDSA was observed at 6 and 24 mo (8.8% vs 7.7% and 15.5% vs 11.1%) and identified pts with ongoing subABMR (AUC = 0.917, 0.809)
Gorbacheva et al[26], 2016		Plasma	mCD4	Rejection	Murine models with sensitized mCD4 T cells had SCr > 1 mg/dL (1.7 ± 0.6 mg/dL by 6–8 d post-transplant) and developed graft failure. At rejection, these recipients had DSA and ↑ frequencies of donor–reactive T cells producing IFN-γ compared with controls
Yazdani et al[27], 2019	95	Plasma	NK gene expression model -> NK cells	Rejection	NK cells predict ABMRavs no rejection (AUC = 0.98); ABMRbvs TCMR (AUC = 0.91) as well as histology: 22/24 biopsies with mvi (g + ptc) had ↑ NK levels (AUC = 0.89) Moreover, activated NK cells had the best predictive capability of graft failure at 1-2 yr (AUC = 0.74). NK cell infiltrationd predicted graft failure independent of histology
Cortes-Cerisuelo et al[28], 2017	23	Plasma	CD28+CD4+	Rejection	CD28+CD4+ T cell frequency is associated with rejection on belatacept based IS

^aP < 0.001 vs controls.

^bP < 0.001 vs TCMR. ^cP < 0.0001 vs biopsies w/o mvi.

^dP < 0.05 vs controls. mBC: Donor reactive memory B-cells; ABMR: Antibody-mediated rejection; DSA: Donor specific antibodies; cABMR: Chronic antibody-mediated rejection; bx: Biopsy; dnDSA: De novo donor specific antibodies; pts: Patients; subABMR: Subclinical ABMR; AUC: Area under the curve; mCD4: Memory cluster of differentiation four; SCr: Serum creatinine; IFN-γ: Interferon gamma; mvi: Microvascular inflammation; NK: Natural killer; TCMR: T cell-mediated rejection; CD28+CD4+: Cluster of differentiation twenty eight and cluster of differentiation four; IS: Immunosuppression.