title: 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.
authors.affiliation: Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Mariana
authors.initials: M
authors.lastname: Urbanova
authors.forename: Irena
authors.initials: I
authors.lastname: Brabcova
authors.forename: Eva
authors.initials: E
authors.lastname: Girmanova
authors.forename: Filip
authors.initials: F
authors.lastname: Zelezny
authors.forename: Ondrej
authors.initials: O
authors.lastname: Viklicky
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology*; D017209:Apoptosis; D001706:Biopsy; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*
chemical_list: D000961:Antilymphocyte Serum; D016328:NF-kappa B; D012333:RNA, Messenger