title: Immunosuppressive drug-free operational immune tolerance in human kidney transplant recipients: Part I. Blood gene expression statistical analysis.
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.
authors.affiliation: Institut de Transplantation Et de la Recherche en Transplantation (ITERT), INSERM, U643, Nantes, F-44000 France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Braud
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
authors.forename: Magali
authors.initials: M
authors.lastname: Giral
authors.forename: Annaïck
authors.initials: A
authors.lastname: Pallier
authors.forename: Joanna
authors.initials: J
authors.lastname: Ashton-Chess
authors.forename: Cecile
authors.initials: C
authors.lastname: Braudeau
authors.forename: Catherine
authors.initials: C
authors.lastname: Chevalier
authors.forename: Alice
authors.initials: A
authors.lastname: Lebars
authors.forename: Jean
authors.initials: J
authors.lastname: Léger
authors.forename: Anne
authors.initials: A
authors.lastname: Moreau
authors.forename: Eugenia
authors.initials: E
authors.lastname: Pechkova
authors.forename: Claudio
authors.initials: C
authors.lastname: Nicolini
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouard
mesh_terms: D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods