TY - JOUR
T1 - Multiparameter immune profiling of operational tolerance in liver transplantation
AU - Martínez-Llordella, M.
AU - Puig-Pey, I.
AU - Orlando, G.
AU - Ramoni, M.
AU - Tisone, G.
AU - Rimola, A.
AU - Lerut, J.
AU - Latinne, D.
AU - Margarit, C.
AU - Bilbao, I.
AU - Brouard, S.
AU - Hernández-Fuentes, M.
AU - Soulillou, J. P.
AU - Sánchez-Fueyo, A.
PY - 2007/2/1
Y1 - 2007/2/1
N2 - Immunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as 'operationally' tolerant. Immune characterization of these patients, however, has not been performed in detail, and we lack tests capable of identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study we have analyzed a variety of biological traits in peripheral blood of operationally tolerant liver recipients in an attempt to define a multiparameter 'fingerprint' of tolerance. Thus, we have performed peripheral blood gene expression profiling and extensive blood cell immunophenotyping on 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals. Microarray profiling identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for γδ T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4 +CD25+ T-cells and Vδ1+ T cells) than either non-tolerant patients or healthy individuals. Our data provide novel mechanistic insight on liver allograft operational tolerance, and constitute a first step in the search for a non-invasive diagnostic signature capable of predicting tolerance before undergoing drug weaning. © 2006 The Authors.
AB - Immunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as 'operationally' tolerant. Immune characterization of these patients, however, has not been performed in detail, and we lack tests capable of identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study we have analyzed a variety of biological traits in peripheral blood of operationally tolerant liver recipients in an attempt to define a multiparameter 'fingerprint' of tolerance. Thus, we have performed peripheral blood gene expression profiling and extensive blood cell immunophenotyping on 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals. Microarray profiling identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for γδ T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4 +CD25+ T-cells and Vδ1+ T cells) than either non-tolerant patients or healthy individuals. Our data provide novel mechanistic insight on liver allograft operational tolerance, and constitute a first step in the search for a non-invasive diagnostic signature capable of predicting tolerance before undergoing drug weaning. © 2006 The Authors.
KW - Alloimmune responses
KW - Expression profiling
KW - Liver transplantation
KW - Regulatory T cells
KW - Tolerance
U2 - 10.1111/j.1600-6143.2006.01621.x
DO - 10.1111/j.1600-6143.2006.01621.x
M3 - Article
SN - 1600-6135
VL - 7
SP - 309
EP - 319
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 2
ER -