Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation

Sofia Christakoudi, Manohursingh Runglall, Paula Mobillo, Irene Rebollo-Mesa, Tjir-Li Tsui, Estefania Nova-Lamperti, Sonia Norris, Yogesh Kamra, Rachel Hilton, Sunil Bhandari, Richard Baker, David Berglund, Sue Carr, David Game, Sian Griffin, Philip A Kalra, Robert Lewis, Patrick B Mark, Stephen D Marks, Iain MacpheeWilliam McKane, Markus G Mohaupt, Ravi Pararajasingam, Sui Phin Kon, Daniel Serón, Manish Sinha, Beatriz Tucker, Ondrej Viklický, Robert I Lechler, Graham M Lord, Daniel Stahl, Maria P Hernandez-Fuentes

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared. Healthy controls (n = 14) were used as reference. The anti-inflammatory glucocorticoid receptor (NR3C1) and the cortisol-activating HSD11B1 and H6PD genes were up-regulated in CR and were lowest in tolerant patients. The pro-inflammatory mineralocorticoid gene (NR3C2) was downregulated in stable and CR patients. NR3C1 was associated with neutrophils and NR3C2 with T-cells. Steroid conversion and receptor genes, alone, enabled classification of tolerant patients and were major contributors to gene-expression signatures of both, tolerance and CR, alongside known tolerance-associated genes, revealing a key role of steroid regulation and response in kidney transplantation.

Original languageEnglish
Pages (from-to)205-216
Number of pages12
JournalMolecular and Cellular Endocrinology
Early online date7 Feb 2018
Publication statusPublished - 15 Sept 2018


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