On the basis of reviewed literature here we describe models of tolerance and summarize the evidence of circulating biomarkers suitable for the assessment of immunological risk in organ transplantation. We focused on results of evaluation of specific peripheral immune cell populations and transcripts in peripheral blood of operationally tolerant liver and kidney transplant recipients. Validation of described markers to define potentially tolerant patients before their use in clinical trials is critical.

• MeSH
• biologické markery krev   MeSH
• lidé MeSH
• monitorování imunologické MeSH
• podskupiny B-lymfocytů fyziologie   MeSH
• T-lymfocyty - podskupiny fyziologie   MeSH
• transplantace jater škodlivé účinky   MeSH
• transplantace ledvin škodlivé účinky   MeSH
• transplantační tolerance fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

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.

• MeSH
• antilymfocytární sérum farmakologie   MeSH
• apoptóza MeSH
• biopsie MeSH
• dospělí MeSH
• down regulace účinky léků   imunologie   fyziologie   MeSH
• imunosupresivní léčba metody   MeSH
• králíci MeSH
• ledviny metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• následné studie MeSH
• NF-kappa B genetika   metabolismus   MeSH
• rejekce štěpu imunologie   patologie   prevence a kontrola   MeSH
• senioři MeSH
• signální transdukce účinky léků   imunologie   fyziologie   MeSH
• stanovení celkové genové exprese MeSH
• transplantace ledvin imunologie   patologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• králíci MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Earlier detection of antibody-mediated rejection of kidney allografts may improve graft outcomes. Profiling of gene expression holds promise for the diagnosis and prognosis of antibody-mediated rejection. Here, we identified 730 patients who received kidney transplants during 2002-2005, including 21 patients (2.9%) who experienced early acute antibody-mediated rejection. We also identified a matched group of 43 patients with early acute T cell-mediated rejection to serve as controls. Compared with patients with T cell-mediated rejection, those with antibody-mediated rejection had significantly higher intrarenal mRNA expression of the cytoprotective heme oxygenase-1 but had lower expression of the regulatory T cell marker forkhead box P3 (FoxP3), the B cell marker CD20, and the chemokine regulated upon activation, normal T cell expressed and secreted (RANTES). T cell infiltration was similar in both groups of patients. Compared with grafts that had a favorable course, those that failed as a result of antibody-mediated rejection had expression profiles suggesting a lack of regulation (less FoxP3, TGF-beta1, RANTES, and CD20). Grafts that failed as a result of T cell-mediated rejection only revealed lower expression of CD20 mRNA. In summary, these data suggest that severe antibody-mediated rejection and T cell-mediated rejection result in graft loss by distinct mechanisms. Molecular phenotypes of early acute rejection might help to identify grafts with poor prognosis, allowing earlier application of additional therapies.

• MeSH
• antigeny CD20 genetika   metabolismus   MeSH
• chemokin CCL5 genetika   metabolismus   MeSH
• dospělí MeSH
• fenotyp MeSH
• forkhead transkripční faktory genetika   metabolismus   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• protilátky imunologie   MeSH
• rejekce štěpu genetika   imunologie   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• stanovení celkové genové exprese MeSH
• studie případů a kontrol MeSH
• T-lymfocyty imunologie   MeSH
• transformující růstový faktor beta1 genetika   metabolismus   MeSH
• transplantace ledvin fyziologie   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH