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Absence of significant overlap in transcriptional patterns between operationally tolerant liver and kidney recipients

ABSTRACT: Transplant recipients spontaneously accepting their grafts in the absence of immunosuppression demonstrate the feasibility of attaining allograft tolerance in humans. Previous studies have identified blood transcriptional and cell phenotypic markers specific for either liver or kidney tolerant recipients, but the two settings have not been directly compared yet employing the same platforms. To identify potential similarities in immune parameters between recipients tolerant to different organs, we analyzed blood samples from tolerant and non-tolerant liver and kidney recipients employing whole genome expression microarrays. Tolerant and non-tolerant liver and kidney recipients differed in their peripheral blood expression patterns, but no significant overlap was observed between the two datasets. This was confirmed at the functional level by employing gene set enrichment analysis.The lack of obvious similarities in immune parameters associated with liver and kidney tolerant recipients implies the involvement of different mechanisms in the two settings and argues against the existence of a common immunological constant of spontaneous operational tolerance in clinical transplantation. The complete database comprised the expression measurements of 54,675 genes for liver and kidney trasplant inmunotolerance groups (n=12 for each group).A group of 12 samples from Healthy volunteer are included.

ORGANISM(S): Homo sapiens

SUBMITTER: Juanjo Lozano

PROVIDER: E-GEOD-22707 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Absence of significant overlap in transcriptional patterns between operationally tolerant liver and kidney recipients

Project description:Transplant recipients spontaneously accepting their grafts in the absence of immunosuppression demonstrate the feasibility of attaining allograft tolerance in humans. Previous studies have identified blood transcriptional and cell phenotypic markers specific for either liver or kidney tolerant recipients, but the two settings have not been directly compared yet employing the same platforms. To identify potential similarities in immune parameters between recipients tolerant to different organs, we analyzed blood samples from tolerant and non-tolerant liver and kidney recipients employing whole genome expression microarrays. Tolerant and non-tolerant liver and kidney recipients differed in their peripheral blood expression patterns, but no significant overlap was observed between the two datasets. This was confirmed at the functional level by employing gene set enrichment analysis.The lack of obvious similarities in immune parameters associated with liver and kidney tolerant recipients implies the involvement of different mechanisms in the two settings and argues against the existence of a common immunological constant of spontaneous operational tolerance in clinical transplantation.

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Transcription profiling of human liver transplant patients reveals a signature that could discriminate tolerant recipients from immunosuppression-dependent patients

Project description:mmunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as âoperationallyâ 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 âfingerprintâ 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 ?d 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 Vd1+ 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. Experiment Overall Design: The complete database comprised the expression measurements of 54 675 genes for nine operationally tolerant (TOL) and eight immunosuppression-dependent (ID) samples.

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