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

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.

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  • Publisher Full Text
  • Authors

    Urbanova M, Brabcova I, Girmanova E, Zelezny F, Viklicky O

    Institution

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

    Source

    Transplantation 93:6 2012 Mar 27 pg 589-96

    MeSH

    Adult
    Aged
    Animals
    Antilymphocyte Serum
    Apoptosis
    Biopsy
    Down-Regulation
    Female
    Follow-Up Studies
    Gene Expression Profiling
    Graft Rejection
    Humans
    Immunosuppression
    Kidney
    Kidney Transplantation
    Male
    Middle Aged
    NF-kappa B
    RNA, Messenger
    Rabbits
    Signal Transduction

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22334040