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Transplantation. 2012 Mar 27;93(6):589-96. doi: 10.1097/TP.0b013e31824491aa.

Differential regulation of the nuclear factor-κB pathway by rabbit antithymocyte globulins in kidney transplantation.

Author information

1
Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Abstract

BACKGROUND:

Induction therapy is associated with excellent short-term kidney graft outcome. The aim of this study was to evaluate differences in the intragraft transcriptome after successful induction therapy using two rabbit antithymocyte globulins.

METHODS:

The expression of 376 target genes involved in tolerance, inflammation, T- and B-cell immune response, and apoptosis was evaluated using the quantitative real-time reverse-transcriptase polymerase chain reaction (2(-ΔΔCt)) method in kidney graft biopsies with normal histological findings and stable renal function, 3 months posttransplantation after induction therapy with Thymoglobulin, ATG-Fresenius S (ATG-F), and a control group without induction therapy.

RESULTS:

The transcriptional pattern induced by Thymoglobulin differed from ATG-F in 18 differentially expressed genes. Down-regulation of genes involved in the nuclear factor-κB pathway (TLR4, MYD88, and CD209), costimulation (CD80 and CTLA4), apoptosis (NLRP1), chemoattraction (CCR10), and dendritic cell function (CLEC4C) was observed in the biopsies from patients treated with Thymoglobulin. A hierarchical clustering analysis clearly separated the Thymoglobulin group from the ATG-F group, while the control group had a similar profile as the Thymoglobulin group.

CONCLUSIONS:

Despite normal morphology in graft biopsy taken 3 months posttransplantation, the intrarenal transcriptome differed in patients treated with induction therapy using different rATGs. In the Thymoglobulin high-risk group, the transcriptome profile was identical to the low-risk group. Therefore, the down-regulation of the nuclear factor-κB pathway after Thymoglobulin induction in vivo is likely to explain the clinical success of this biologic.

PMID:
22334040
DOI:
10.1097/TP.0b013e31824491aa
[Indexed for MEDLINE]

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