Tolerance in liver transplantation: Biomarkers and clinical relevance

Table 1 Biomarkers of tolerance in liver transplantation

Biomarker	Description	Study before or during IS withdrawal	Ref.
Dendritic cells
pCD/mCD ratio	Tolerant patients have elevated pDC/mDC ratio. No differences between tolerant patients vs healthy controls	No	[134,150]
mDCs/pCD ratio	Elevated mDC/pCD associated with late rejection	No	[151]
PD-L1/CD86 ratio	Elevated PD-L1/CD86 expression on DCs in tolerant patients	No	[152]
DC HLA-G expression	Elevated on mDC	No	[153]
T cells
Regulatory T cells	Increase of peripheral CD4+CD25high cells and RNA FoxP3 over time during weaning	Yes	[40,43,44,133]
	Increase in T regs in liver biopsy of tolerant patients
Natural killer	Increase in Tolerant patients	Yes	[154]
Soluble factors
Serum HLA-G	Normal or elevated serum HLA-G levels associated to normal liver	No	[155-157]
Anti-donor antibodies	Absent in tolerant patients	No	[150]
Cell proliferation
Phytohemagglutinin SI	SI < 20 and > 10 yr since LT 100% tolerance	Yes	[158]
Genetic profile
Cytokine gene polymorphism	Low TNF-alpha and high/intermediate IL-10 production in OT	No	[159]
Gene transcripts	Enriched from NK, CD4+CD25+ FoxP3+, γδTCR+ and δ1TCR+	No	[42,43,160]
Genes related to iron homeostasis in liver graft	Enriched in tolerant patients (CDHR2, MIF, PEBP1, SOCS1, TRF)	Yes	[140]

DC: Dendritic cell; mDC: Monocytoid dendritic cell; LT: Liver transplantation; pDC: plasmacytoid dendritic cell; SI: Stimulation index.