Nejvíce citovaný článek - PubMed ID 23711167
Cytomegalovirus (CMV) infection is associated with allograft rejection but the mechanisms behind are poorly defined yet. Although cross-reactivity of T cells to alloantigen and CMV has been hypothesized, direct evidence in patients is lacking. In this observational cohort study, we tested the pre-transplant effector/memory T cell response to CMV peptide pools and alloantigen in 78 living donor/recipient pairs using the interferon-gamma Enzyme-Linked ImmunoSpot (ELISPOT) assay. To prove the hypothesis of cross-reactivity, we analyzed by applying next-generation sequencing the T cell receptor ß (TCR- ß) repertoire of CMV- and alloantigen-reactive T cells enriched from peripheral pre-transplant blood of 11 CMV-seropositive and HLA class I mismatched patients. Moreover, the TCR-repertoire was also analyzed in the allograft biopsies of those patients. There was a significant association between the presence of pre-transplant CMV immediate-early protein 1 (IE-1)-specific effector/memory T cells and acute renal allograft rejection and function (p = 0.01). Most importantly, we revealed shared TCR-ß sequences between CMV-IE1 and donor alloantigen-reactive T cells in all pre-transplant peripheral blood samples analyzed in CMV-seropositive patients who received HLA class I mismatched grafts. Identical TCR sequences were also found in particular in post-transplant allograft biopsies of patients with concomitant CMV infection and rejection. Our data show the presence of functional, cross-reactive T cells and their clonotypes in peripheral blood and in kidney allograft tissue. It is therefore likely that CMV-donor cross-reactivity as well as CMV specific T cell elicited inflammation is involved in the processes that affect allograft outcomes.
- Klíčová slova
- ELISPOT, TCR repertoire, cross-reactivity, cytomegalovirus, heterologous immunity, kidney transplantation, rejection,
- MeSH
- alografty MeSH
- biopsie MeSH
- cytomegalovirové infekce * etiologie genetika imunologie patologie MeSH
- Cytomegalovirus imunologie MeSH
- dospělí MeSH
- imunologická paměť * MeSH
- isoantigeny genetika imunologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- receptory antigenů T-buněk alfa-beta * imunologie MeSH
- T-lymfocyty * mikrobiologie patologie MeSH
- transplantace ledvin * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- isoantigeny MeSH
- receptory antigenů T-buněk alfa-beta * MeSH
BACKGROUND AND OBJECTIVES: Both valganciclovir and high-dose valacyclovir are recommended for cytomegalovirus prophylaxis after renal transplantation. A head-to-head comparison of both regimens is lacking. The objective of the study was to compare valacyclovir prophylaxis with valganciclovir, which constituted the control group. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: In a randomized, open-label, single-center trial, recipients of renal transplants (recipient or donor cytomegalovirus-seropositive) were randomly allocated (1:1) to 3-month prophylaxis with valacyclovir (2 g four times daily) or valganciclovir (900 mg daily). Enrollment occurred from November of 2007 to April of 2012. The primary end points were cytomegalovirus DNAemia and biopsy-proven acute rejection at 12 months. Analysis was by intention to treat. RESULTS: In total, 119 patients were assigned to valacyclovir (n=59) or valganciclovir prophylaxis (n=60). Cytomegalovirus DNAemia developed in 24 (43%) of 59 patients in the valacyclovir group and 18 (31%) of 60 patients in the valganciclovir group (adjusted hazard ratio, 1.35; 95% confidence interval, 0.71 to 2.54; P=0.36). The incidence of cytomegalovirus disease was 2% with valacyclovir and 5% with valganciclovir prophylaxis (adjusted hazard ratio, 0.21; 95% confidence interval, 0.01 to 5.90; P=0.36). Significantly more patients with valacyclovir prophylaxis developed biopsy-proven acute rejection (18 of 59 [31%] versus 10 of 60 [17%]; adjusted hazard ratio, 2.49; 95% confidence interval, 1.09 to 5.65; P=0.03). The incidence of polyomavirus viremia was higher in the valganciclovir group (18% versus 36%; adjusted hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.96; P=0.04). CONCLUSIONS: Valganciclovir shows no superior efficacy in cytomegalovirus DNAemia prevention compared with valacyclovir prophylaxis. However, the risk of biopsy-proven acute rejection is higher with valacyclovir.
- Klíčová slova
- cytomegalovirus, prevention, renal transplantation, valacyclovir, valganciclovir,
- MeSH
- acyklovir aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- akutní nemoc MeSH
- analýza podle původního léčebného záměru MeSH
- antivirové látky aplikace a dávkování škodlivé účinky MeSH
- biologické markery krev MeSH
- biopsie MeSH
- časové faktory MeSH
- cytomegalovirové infekce diagnóza imunologie prevence a kontrola virologie MeSH
- Cytomegalovirus účinky léků genetika MeSH
- DNA virů krev MeSH
- dospělí MeSH
- ganciklovir aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- imunosupresiva terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- přežívání štěpu účinky léků MeSH
- rejekce štěpu diagnóza imunologie prevence a kontrola MeSH
- rozvrh dávkování léků MeSH
- transplantace ledvin škodlivé účinky MeSH
- valaciclovir MeSH
- valganciklovir MeSH
- valin aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- virová nálož MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- acyklovir MeSH
- antivirové látky MeSH
- biologické markery MeSH
- DNA virů MeSH
- ganciklovir MeSH
- imunosupresiva MeSH
- valaciclovir MeSH
- valganciklovir MeSH
- valin MeSH
