Immunosuppressive drug-free operational immune tolerance in human kidney transplant recipients: Part I. Blood gene expression statistical analysis |
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Authors: | Braud Christophe Baeten Dominique Giral Magali Pallier Annaïck Ashton-Chess Joanna Braudeau Cecile Chevalier Catherine Lebars Alice Léger Jean Moreau Anne Pechkova Eugenia Nicolini Claudio Soulillou Jean-Paul Brouard Sophie |
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Institution: | Institut de Transplantation Et de la Recherche en Transplantation (ITERT), INSERM, U643, Nantes, F-44000 France. |
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Abstract: | Survival of solid organ grafts depends on life-long immunosuppression, which results in increased rates of infection and malignancy. Induction of tolerance to allografts would represent the optimal solution for controlling both chronic rejection (CR) and side effects of immunosuppression. Although spontaneous "operational tolerance" can occur in human kidney transplantation, the lack of noninvasive peripheral blood biological markers of this rare phenomenon precludes the identification of potentially tolerant patients in whom immunosuppression could be tapered as well as the development of new tolerance inducing strategies. Here, the potential of high throughput microarray technology to decipher complex pathologies allowed us to study the peripheral blood specific gene expression profile and corresponding EASE molecular pathways associated to operational tolerance in a cohort of human kidney graft recipients. In comparison with patients with CR, tolerant patients displayed a set of 343 differentially expressed genes, mainly immune and defense genes, in their peripheral blood mononuclear cells (PBMC), of which 223 were also different from healthy volunteers. Using the expression pattern of these 343 genes, we were able to classify correctly >80% of the patients in a cross-validation experiment and classified correctly all of the samples over time. Collectively, this study identifies a unique PBMC gene signature associated with human operational tolerance in kidney transplantation by a classical statistical microarray analysis and, in the second part, by a nonstatistical analysis. |
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Keywords: | gene expression DNA microarray kidney transplant transplant tolerance chronic rejection |
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