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Multiparameter immune profiling of operational tolerance in liver transplantation

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Martínez-Llordella, Marc Lerut, Jan [UCL] Puig-Pey, I. Orlando, Giuseppe [UCL] Ramoni, M. Latinne, Dominique [UCL] Soulillou, J. -P.

Immunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as 'operationally' tolerant.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 gamma delta 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 V delta 1(+) 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.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2007
Language Anglais
Journal information "American Journal of Transplantation" - Vol. 7, no. 2, p. 309-19 (2007)
Peer reviewed yes
Publisher Blackwell Publishing (Oxford)
issn 1600-6135
e-issn 1600-6143
Publication status Publié
Affiliations UCL - MD/CHIR - Département de chirurgie
UCL - (SLuc) Service de chirurgie et transplantation abdominale
UCL - (SLuc) Service de biologie hématologique
MESH Subject Transplantation Tolerance - genetics ; Transplantation Immunology - genetics ; T-Lymphocytes, Regulatory - immunology ; Receptors, Antigen, T-Cell, gamma-delta - genetics ; Predictive Value of Tests ; Middle Aged ; Liver Transplantation - immunology - pathology ; Interleukin-2 Receptor alpha Subunit - genetics ; Immunosuppressive Agents - administration & dosage ; Immunophenotyping ; Immune Tolerance ; Humans ; Hepacivirus - genetics - pathogenicity ; Graft Rejection - diagnosis - genetics - immunology ; Gene Expression Profiling ; DNA, Viral - genetics ; DNA - genetics ; Antigens, CD4 - genetics
Keywords alloimmune responses ; expression profiling ; liver transplantation ; regulatory T cells ; tolerance
Links
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Bibliographic reference Martínez-Llordella, Marc ; Lerut, Jan ; Puig-Pey, I. ; Orlando, Giuseppe ; Ramoni, M. ; et. al. Multiparameter immune profiling of operational tolerance in liver transplantation. In: American Journal of Transplantation, Vol. 7, no. 2, p. 309-19 (2007)
Permanent URL http://hdl.handle.net/2078.1/37857