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Series GSE47097 Query DataSets for GSE47097
Status Public on May 21, 2013
Title Increased metallothionein expression reflects steroid resistance in renal allograft recipients.
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Steroid-refractory acute rejection is a risk factor for inferior renal allograft outcome. We aimed to gain insight into the mechanisms underlying steroid resistance by identifying novel molecular markers of steroid-refractory acute rejection.
Eighty-three kidney transplant recipients (1995-2005), who were treated with methylprednisolone during a first acute rejection episode, were included in this study. Gene expression patterns were investigated in a discovery cohort of 36 acute rejection biopsies, and verified in a validation cohort of 47 acute rejection biopsies.
In the discovery set, expression of metallothioneins (MT) was significantly (P<0.000001) associated with decreased response to steroid treatment. Multivariate analysis resulted in a predictive model containing MT-1 as an independent covariate (AUC=0.88, P<0.0000001). In the validation set, MT-1 expression was also significantly associated with steroid resistance (P=0.029). Metallothionein expression was detected in macrophages and tubular epithelial cells. Parallel to the findings in patients, in vitro experiments of peripheral blood mononuclear cells from 11 donors showed that non-response to methylprednisolone treatment is related to highly elevated MT levels.
High expression of metallothioneins in renal allografts is associated with resistance to steroid treatment. Metallothioneins regulate intracellular concentrations of zinc, through which they may diminish the zinc-requiring anti-inflammatory effect of the glucocorticoid receptor.
 
Overall design Transcriptional profiles of 40 renal allograft biopsy samples were analyzed using Illumina HumanRef-8 v3.0 BeadChips (Illumina, San Diego, CA). Expression profiles were investigated in total RNA isolated from biopsy samples of 18 patients with steroid responsive acute rejection and 18 patients with steroid resistant acute rejection. Four biopsies, taken during acute decrease of graft function but with no histomorphologic indication of rejection, were included as controls.
 
Contributor(s) Rekers NV, Bajema IM, Mallat MJ, Anholts JD, de Vaal YJ, Zandbergen M, Haasnoot GW, van Zwet EW, de Fijter JW, Claas FH, Eikmans M
Citation(s) 23763497
Submission date May 20, 2013
Last update date Mar 20, 2017
Contact name Niels Rekers
E-mail(s) nielsrekers@hotmail.com
Organization name Leiden University Medical Center
Department Immunohematology and Blood Transfusion
Street address Achter Nieuwstraat
City Bodegraven
State/province Nederland
ZIP/Postal code 2411EN
Country Netherlands
 
Platforms (1)
GPL6883 Illumina HumanRef-8 v3.0 expression beadchip
Samples (40)
GSM1144714 4669609027_A
GSM1144715 4669609027_B
GSM1144716 4669609027_C
Relations
BioProject PRJNA203546

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE47097_RAW.tar 3.9 Mb (http)(custom) TAR
GSE47097_non_normalized.txt.gz 6.7 Mb (ftp)(http) TXT
Processed data included within Sample table

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