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 Macphee; William 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

doi:10.1016/j.mce.2018.01.021

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 journal › Article › peer-review

11 Citations (Scopus)

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.

Original language	English
Pages (from-to)	205-216
Number of pages	12
Journal	Molecular and Cellular Endocrinology
Volume	473
Early online date	7 Feb 2018
DOIs	https://doi.org/10.1016/j.mce.2018.01.021
Publication status	Published - 15 Sept 2018

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10.1016/j.mce.2018.01.021

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Christakoudi, S., Runglall, M., Mobillo, P., Rebollo-Mesa, I., Tsui, T.-L., Nova-Lamperti, E., Norris, S., Kamra, Y., Hilton, R., Bhandari, S., Baker, R., Berglund, D., Carr, S., Game, D., Griffin, S., Kalra, P. A., Lewis, R., Mark, P. B., Marks, S. D., ... Hernandez-Fuentes, M. P. (2018). Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation. Molecular and Cellular Endocrinology, 473, 205-216. https://doi.org/10.1016/j.mce.2018.01.021

@article{3e0c99f9197a41c4b630877d7ad9a0b8,

title = "Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation",

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.",

author = "Sofia Christakoudi and Manohursingh Runglall and Paula Mobillo and Irene Rebollo-Mesa and Tjir-Li Tsui and Estefania Nova-Lamperti and Sonia Norris and Yogesh Kamra and Rachel Hilton and Sunil Bhandari and Richard Baker and David Berglund and Sue Carr and David Game and Sian Griffin and Kalra, {Philip A} and Robert Lewis and Mark, {Patrick B} and Marks, {Stephen D} and Iain Macphee and William McKane and Mohaupt, {Markus G} and Ravi Pararajasingam and Kon, {Sui Phin} and Daniel Ser{\'o}n and Manish Sinha and Beatriz Tucker and Ondrej Viklick{\'y} and Lechler, {Robert I} and Lord, {Graham M} and Daniel Stahl and Hernandez-Fuentes, {Maria P}",

year = "2018",

month = sep,

day = "15",

doi = "10.1016/j.mce.2018.01.021",

language = "English",

volume = "473",

pages = "205--216",

journal = "Molecular and Cellular Endocrinology",

issn = "0303-7207",

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}

Christakoudi, S , Runglall, M , Mobillo, P , Rebollo-Mesa, I, Tsui, T-L, Nova-Lamperti, E , Norris, S , Kamra, Y, Hilton, R, Bhandari, S, Baker, R, Berglund, D, Carr, S, Game, D, Griffin, S, Kalra, PA, Lewis, R, Mark, PB, Marks, SD, Macphee, I, McKane, W, Mohaupt, MG, Pararajasingam, R, Kon, SP, Serón, D, Sinha, M, Tucker, B, Viklický, O, Lechler, RI , Lord, GM , Stahl, D & Hernandez-Fuentes, MP 2018, 'Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation', Molecular and Cellular Endocrinology, vol. 473, pp. 205-216. https://doi.org/10.1016/j.mce.2018.01.021

TY - JOUR

T1 - Steroid regulation

T2 - An overlooked aspect of tolerance and chronic rejection in kidney transplantation

AU - Christakoudi, Sofia

AU - Runglall, Manohursingh

AU - Mobillo, Paula

AU - Rebollo-Mesa, Irene

AU - Tsui, Tjir-Li

AU - Nova-Lamperti, Estefania

AU - Norris, Sonia

AU - Kamra, Yogesh

AU - Hilton, Rachel

AU - Bhandari, Sunil

AU - Baker, Richard

AU - Berglund, David

AU - Carr, Sue

AU - Game, David

AU - Griffin, Sian

AU - Kalra, Philip A

AU - Lewis, Robert

AU - Mark, Patrick B

AU - Marks, Stephen D

AU - Macphee, Iain

AU - McKane, William

AU - Mohaupt, Markus G

AU - Pararajasingam, Ravi

AU - Kon, Sui Phin

AU - Serón, Daniel

AU - Sinha, Manish

AU - Tucker, Beatriz

AU - Viklický, Ondrej

AU - Lechler, Robert I

AU - Lord, Graham M

AU - Stahl, Daniel

AU - Hernandez-Fuentes, Maria P

PY - 2018/9/15

Y1 - 2018/9/15

N2 - 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.

AB - 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.

U2 - 10.1016/j.mce.2018.01.021

DO - 10.1016/j.mce.2018.01.021

M3 - Article

C2 - 29427591

SN - 0303-7207

VL - 473

SP - 205

EP - 216

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

ER -

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

Abstract

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