BACKGROUND: There is high medical need for safe long-term immunosuppression monotherapy in kidney transplantation. Selective targeting of post-transplant alloantigen-(re)activated effector-T cells by anti-TNF antibodies after global T cell depletion may allow safe drug minimization, however, it is unsolved what might be the best maintenance monotherapy. METHODS: In this open, prospective observational single-centre trial, 20 primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (d0/d1) followed by 5 mg/kg Infliximab (d2). For 14 days all patients received only tacrolimus, then they were allocated to either receive tacrolimus (TAC, n = 13) or sirolimus (SIR, n = 7) monotherapy, respectively. Protocol biopsies and extensive immune monitoring were performed and patients were followed-up for 60 months. RESULTS: TAC-monotherapy resulted in excellent graft survival (5yr 92%, 95%CI: 56.6-98.9) and function, normal histology, and no proteinuria. Immune monitoring revealed low intragraft inflammation (urinary IP-10) and hints for the development of operational tolerance signature in the TAC- but not SIR-group. Remarkably, the TAC-monotherapy was successful in all five presensitized (ELISPOT+) patients. However, recruitment into SIR-arm was stopped (after n = 7) because of high incidence of proteinuria and acute/chronic rejection in biopsies. No opportunistic infections occurred during follow-up. CONCLUSIONS: In conclusion, our novel fast-track TAC-monotherapy protocol is likely to be safe and preliminary results indicated an excellent 5-year outcome, however, a full-scale study will be needed to confirm our findings. TRIAL REGISTRATION: EudraCT Number: 2006-003110-18.

• MeSH
• antigen CD52 MeSH
• antigeny nádorové MeSH
• biologické markery metabolismus   MeSH
• CD antigeny MeSH
• dospělí MeSH
• glykoproteiny antagonisté a inhibitory   MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• monitorování imunologické MeSH
• prospektivní studie MeSH
• rejekce štěpu farmakoterapie   etiologie   MeSH
• sirolimus terapeutické užití   MeSH
• stanovení celkové genové exprese MeSH
• takrolimus terapeutické užití   MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• transplantace ledvin škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• pozorovací studie MeSH
• Názvy látek
• antigen CD52 MeSH
• antigeny nádorové MeSH
• biologické markery MeSH
• CD antigeny MeSH
• CD52 protein, human MeSH Prohlížeč
• glykoproteiny MeSH
• imunosupresiva MeSH
• sirolimus MeSH
• takrolimus MeSH
• TNF-alfa MeSH

BACKGROUND: Induction therapy can improve kidney transplantation (KTx) outcomes, but little is known about the mechanisms underlying its effects. METHODS: The mRNA levels of T cell-related genes associated with tolerance or rejection (CD247, GZMB, PRF1, FOXP3, MAN1A1, TCAIM, and TLR5) and lymphocyte subpopulations were monitored prospectively in the peripheral blood of 60 kidney transplant recipients before and 7, 14, 21, 28, 60, 90 days, 6 months, and 12 months after KTx. Patients were treated with calcineurin inhibitor-based triple immunosuppression and induction with rabbit anti-thymocyte globulin (rATG, n = 24), basiliximab (n = 17), or without induction (no-induction, n = 19). A generalized linear mixed model with gamma distribution for repeated measures, adjusted for rejection, recipient/donor age and delayed graft function, was used for statistical analysis. RESULTS: rATG treatment caused an intense reduction in all T cell type population and natural killer (NK) cells within 7 days, then a slow increase and repopulation was observed. This was also noticed in the expression levels of CD247, FOXP3, GZMB, and PRF1. The basiliximab group exhibited higher CD247, GZMB, FOXP3 and TCAIM mRNA levels and regulatory T cell (Treg) counts than the no-induction group. The levels of MAN1A1 and TLR5 mRNA expressions were increased, whereas TCAIM decreased in the rATG group as compared with those in the no-induction group. CONCLUSION: The rATG induction therapy was associated with decreased T and NK cell-related transcript levels and with upregulation of two rejection-associated transcripts (MAN1A1 and TLR5) shortly after KTx. Basiliximab treatment was associated with increased absolute number of Treg cells, and increased level of FOXP3 and TCAIM expression.

• MeSH
• antigeny CD3 genetika   MeSH
• antilymfocytární sérum terapeutické užití   MeSH
• basiliximab MeSH
• dospělí MeSH
• exprese genu účinky léků   MeSH
• forkhead transkripční faktory genetika   MeSH
• granzymy genetika   MeSH
• imunologická tolerance účinky léků   genetika   MeSH
• imunosupresiva terapeutické užití   MeSH
• imunosupresivní léčba metody   MeSH
• indukční chemoterapie metody   MeSH
• inhibitory kalcineurinu terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mannosidasy genetika   MeSH
• messenger RNA krev   MeSH
• mladý dospělý MeSH
• monoklonální protilátky terapeutické užití   MeSH
• NKT buňky účinky léků   imunologie   MeSH
• perforin genetika   MeSH
• počet lymfocytů MeSH
• prospektivní studie MeSH
• regulační T-lymfocyty účinky léků   imunologie   MeSH
• rejekce štěpu genetika   imunologie   prevence a kontrola   MeSH
• rekombinantní fúzní proteiny terapeutické užití   MeSH
• senioři MeSH
• transplantace ledvin metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD3 MeSH
• antilymfocytární sérum MeSH
• basiliximab MeSH
• CD3 antigen, zeta chain MeSH Prohlížeč
• forkhead transkripční faktory MeSH
• FOXP3 protein, human MeSH Prohlížeč
• granzymy MeSH
• GZMB protein, human MeSH Prohlížeč
• imunosupresiva MeSH
• inhibitory kalcineurinu MeSH
• mannosidasy MeSH
• mannosyl-oligosaccharide 1,2-alpha-mannosidase MeSH Prohlížeč
• messenger RNA MeSH
• monoklonální protilátky MeSH
• perforin MeSH
• PRF1 protein, human MeSH Prohlížeč
• rekombinantní fúzní proteiny MeSH