학술논문
Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation.
Document Type
Article
Author
Mobillo, Paula; Nova-Lamperti, Estefania; Norris, Sonia; Kamra, Yogesh; Christakoudi, Sofia; Rebollo-Mesa, Irene; Lechler, Robert I.; Hernandez-Fuentes, Maria P.; Lord, Graham M.; Tsui, Tjir-Li; Kalra, Philip A.; Lewis, Robert; Mark, Patrick B.; Marks, Stephen D.; Macphee, Iain; McKane, William; Mohaupt, Markus G.; Pararajasingam, Ravi; Kon, Sui Phin; Tucker, Beatriz
Source
Subject
*STEROID drugs
*ANTIANDROGENS
*DELEGATED legislation
*KIDNEY abnormalities
*TRANSPLANTATION immunology
*
*
*
*
Language
ISSN
0303-7207
Abstract
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. [ABSTRACT FROM AUTHOR]