Identification of a gene expression profile associated with operational tolerance among a selected group of stable kidney transplant patients.

Despite their utility, immunosuppressive treatments have numerous side effects, including infectious complications, malignancies and metabolic disorders, all of which contribute to long-term graft loss. In addition to the development of new pharmaceutical products with reduced toxicity and more comfortable modes of administration, tailoring immunosuppression according to the immune status of each patient would represent a significant breakthrough. Gene expression profiling has been shown to be a clinically relevant monitoring tool. In this paper, we have assessed the overall long-term kidney transplant outcome and attempted to identify operationally tolerant-like patients among recipients with stable clinical status at least 5 years post-transplantation. We thus measured a combination of noninvasive blood biomarkers of operational tolerance in a cohort of 144 stable patients and showed that only 3.5% exhibited a gene expression profile of operational tolerance, suggesting that such a profile can be detected under immunosuppressive therapy but that its frequency is low in kidney transplant recipients when compared with liver transplant recipients. We suggest that a rational approach to patient selection, based on a combination of clinical and biological characteristics, may help to provide a safer method for identification of patients potentially suitable for immunosuppressive drug weaning procedures.

Transcriptome profiling uncovers metabolic and regulatory processes occurring during the transition from desiccation-sensitive to desiccation-tolerant stages in Medicago truncatula seeds.

To investigate regulatory processes and protective mechanisms leading to desiccation tolerance (DT) in seeds, 16086-element microarrays were used to monitor changes in the transcriptome of desiccation-sensitive 3-mm-long radicles of Medicago truncatula seeds at different time points during incubation in a polyethylene glycol (PEG) solution at -1.7 MPa, resulting in a gradual re-establishment of DT. Gene profiling was also performed on embryos before and after the acquisition of DT during maturation. More than 1300 genes were differentially expressed during the PEG incubation. A large number of genes involved in C metabolism are expressed during the re-establishment of DT. Quantification of C reserves confirms that lipids, starch and oligosaccharides were mobilised, coinciding with the production of sucrose during the early osmotic adjustment. Several clusters of gene profiles were identified with different time-scales. Genes expressed early during the PEG incubation belonged to classes involved in early stress and adaptation responses. Interestingly, several regulatory genes typically expressed during abiotic/drought stresses were also upregulated during maturation, arguing for the partial overlap of ABA-dependent and -independent regulatory pathways involved in both drought and DT. At later time points, in parallel to the re-establishment of DT, upregulated genes are comparable with those involved in late seed maturation. Concomitantly, a massive repression of genes belonging to numerous classes occurred, including cell cycle, biogenesis, primary and energy metabolism. The re-establishment of DT in the germinated radicles appears to concur with a partial return to the quiescent state prior to germination.