Abstract：
BACKGROUND:While acute neurotoxic side effects of calcineurin inhibitors (CNI) are well-known, data upon long-term effects on brain structure and function are sparse. We hypothesize that long-term CNI therapy affects the neuroimmune system, thereby, increasing the risk of neurodegeneration. Here, we measured the impact of CNI therapy on plasma levels of brain- and T cell-derived cytokines in a cohort of patients after liver transplantation (LT). METHODS:Levels of T cell-mediated cytokines (e.g. Interferon-γ (IFN-γ)) and brain-derived cytokines (e.g. brain derived neurotrophic factor (BDNF), platelet derived growth factor (PDGF)) were measured by multiplex assays in plasma of 82 patients about 10 years after LT (17 with CNI free, 35 with CNI low dose, 30 with standard dose CNI immunosuppression) and 33 healthy controls. Data were related to psychometric test results and parameters of cerebral magnetic resonance imaging. RESULTS:IFN-γ levels were significantly higher in the CNI free LT patient group (p=0.027) compared to healthy controls. BDNF levels were significantly lower in LT patients treated with CNI (CNI low: p<0.001; CNI standard: p=0.016) compared to controls. PDGF levels were significantly lower in the CNI low dose group (p=0.004) and for PDGF-AB/BB also in the CNI standard dose group (p=0.029) compared to controls. BDNF and PDGF negatively correlated with cognitive function and brain volume (p<0.05) in the CNI low dose group. CONCLUSION:Our results imply that long-term treatment with CNI suppresses BDNF and PDGF expression, both crucial for neuronal signaling, cell survival and synaptic plasticity and thereby may lead to cognitive dysfunction and neurodegeneration.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Dirks M,Pflugrad H,Tryc AB,Schrader AK,Ding X,Lanfermann H,Jäckel E,Schrem H,Beneke J,Barg-Hock H,Klempnauer J,Falk CS,Weissenborn Kdoi
10.1016/j.trim.2019.101248subject
Has Abstractpub_date
2020-02-01 00:00:00pages
101248eissn
0966-3274issn
1878-5492pii
S0966-3274(19)30066-8journal_volume
58pub_type
杂志文章abstract：BACKGROUND:Results from published studies on the association of donor or recipient IL-6 -174G/C (rs1800795) polymorphism with acute rejection (AR) of renal allograft are conflicting. We performed a meta-analysis to estimate the possible association. METHODS:Studies were identified by searching PUBMED and EMBASE until ...
journal_title：Transplant immunology
pub_type： 杂志文章,meta分析,评审
doi：10.1016/j.trim.2011.10.003
更新日期：2012-01-01 00:00:00
abstract：:Previous work on the facilitation of xenogeneic and allogeneic bone marrow engraftment in irradiated mice and dogs with transferrins allowed the development of a model for induction of an apparently durable state of immunological unresponsiveness or 'tolerance' in chemically immunosuppressed mice. The system is based ...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/s0966-3274(96)80051-7
更新日期：1996-12-01 00:00:00
abstract：:Autoimmune diseases are the result of an interplay between predisposing genes and triggering environmental factors, leading to loss of self-tolerance and an immune-mediated destruction of autologous cells and/or tissues. Genes in the HLA complex are among the strongest predisposing genetic factors. The HLA complex gen...
journal_title：Transplant immunology
pub_type： 杂志文章,评审
doi：10.1016/j.trim.2005.03.021
更新日期：2005-08-01 00:00:00
abstract：BACKGROUND:So far, the ImmuKnow Immune Cell Function Assay (Cylex, Inc., Columbia, MD, USA) has been used to assess risks of infection and rejection in transplant patients. We hypothesized that the ImmuKnow assay might be used for mortality screening in transplant patients overall. METHODS:In the period of February 20...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2010.12.005
更新日期：2011-05-01 00:00:00
abstract：:Rabbit anti-rat thymoglobulin (rATG) administered to donors with brain death (BD) may improve organs quality. We explored the effects of rATG administered to BD donors in the histology of heart, lungs and small bowel in a rat experimental model. Animals were randomly assigned to 3 groups: V (n=5) no BD, 2h ventilation...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2013.04.002
更新日期：2013-06-01 00:00:00
abstract：BACKGROUND:The liver is an immunological organ containing a large number of T, NK and NKT cells, but little is known about intrahepatic immunity after LTx. Here, we investigated whether the distribution of T, NK and CD3(+)CD56(+)NKT cells is altered in transplanted livers under different circumstances. METHODS:Core bi...
journal_title：Transplant immunology
pub_type： 临床试验,杂志文章
doi：10.1016/j.trim.2011.05.006
更新日期：2011-07-01 00:00:00
abstract：:Keratinocytes are activated to express MHC class II and ICAM-1 molecules during cutaneous inflammatory reactions. It is controversial how the interaction between these 'nonprofessional' antigen presenting cells (APC) and infiltrating T cells affects the local inflammatory response. To address this issue we analyzed wh...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/0966-3274(93)90059-h
更新日期：1993-01-01 00:00:00
abstract：BACKGROUND:We recently reported that autoreactive antibody (Ab) against nuclear histone H1 had been identified as an immunosuppressive factor in a rat tolerogenic orthotopic liver transplantation (OLT) model. The present study aimed to determine whether the up-regulation of antihistone H1 Ab by histone H1 vaccination l...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2007.01.003
更新日期：2007-04-01 00:00:00
abstract：BACKGROUND:Tim-3 was recently described as a Th1-specific molecule, participating in the regulation of immune responses and in the induction of allograft tolerance. Here, we studied Tim-3 mRNA expression together with molecular markers of T-cell activation and cytotoxicity, in rejected human kidney grafts. METHODS:Twe...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2006.11.003
更新日期：2007-04-01 00:00:00
abstract：BACKGROUND:Xenotransplantation is an appealing alternative to human allotransplantation because of a worldwide shortage of organs. One of the obstacles for xenografts is cellular rejection by the innate immune system, comprised of NK cells, monocytes, and macrophages. In this study the inhibitory function of HLA-G1, a ...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2014.12.004
更新日期：2015-03-01 00:00:00
abstract：AIM:To investigate the influence of immunosuppressants on the fertility of males who undergo renal transplantation as well as on the immune function of their offspring. METHODS:A survey was performed on the fertility of 164 male renal transplant recipients who underwent a long-term treatment with cyclosporine A (CsA),...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2009.10.001
更新日期：2009-12-01 00:00:00
abstract：:C3H mice were immunized by repeated skin grafting with B10.BR tail skin. Ten days after the last immunization mice received 100 micrograms (intravenously) of a variety of different monoclonal antibodies (mAbs: anti-ICAM-1, -LFA-1, -VCAM-1, -VLA-4), alone or in combination, followed by further B10.BR skin grafts. Contr...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/0966-3274(95)80007-7
更新日期：1995-03-01 00:00:00
abstract：:This study provides data on HLA-A, -B, and -DRB1 frequencies among 861 end-stage renal disease (ESRD) patients from Croatia and estimates the benefit of the kidney exchange program by comparing HLA distribution and assessing HLA mismatches (MMs) within a group of ESRD patients who received kidney grafts from 707 cadav...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2020.101318
更新日期：2020-10-01 00:00:00
abstract：BACKGROUND:Graft-versus-host disease is one of the major complications after allogeneic bone marrow transplantation, but it is not easy to anticipate the onset. Cytokines released by type 1 T helper cells are thought to play a pivotal role in acute graft-versus-host disease aGVHD. The ability to predict the likely occu...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2005.10.002
更新日期：2006-01-01 00:00:00
abstract：:We investigated the immunosuppressive effects of the dihydroortate dehydrogenase (DHODH) inhibitor compounds ABR-222417 and ABR-224050 from Active Biotech (Sweden). We verified the inhibitory effects of these compounds on the proliferation of CD4(+) and CD8(+) T-cells in vivo by using superantigen staphylococcus enter...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2010.05.005
更新日期：2010-08-01 00:00:00
abstract：BACKGROUND:Molecules of the innate immune response are increasingly recognized as important mediators in allograft injury during and after kidney transplantation. We therefore aimed to establish the relationship between the expression of these genes at implantation, during an acute rejection (AR) and on graft outcome. ...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2018.02.009
更新日期：2018-06-01 00:00:00
abstract：:The induction of antigen-specific T cell tolerance and its maintenance in the periphery are critical for the immune system to prevent autoaggressive immune responses. Our current state of knowledge about the immunoregulatory mechanisms responsible for T cell tolerance in the periphery offers new possibilities for immu...
journal_title：Transplant immunology
pub_type： 杂志文章,评审
doi：10.1016/S0966-3274(03)00057-1
更新日期：2003-07-01 00:00:00
abstract：:The effect of blocking the expression of the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in a graft by an antibody, and immunohistochemical changes in the graft were monitored, using a rat small intestinal transplantation model. Dark Agouti (DA) rat small intestines were heterotopically transplanted into Lew...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2007.01.011
更新日期：2007-06-01 00:00:00
abstract：BACKGROUND:Pigs are frequently used as animal models for experiments in the surgical field, including allo- and xeno-transplantation. Regeneration studies, including studies dealing with human- and monkey-induced pluripotent stem cells (iPSC), have gradually progressed, with pigs sometimes being used as the scaffold. H...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2016.12.002
更新日期：2017-02-01 00:00:00
abstract：AIMS:Chronic renal allograft loss is still an unsolved problem in kidney transplantation. We evaluated the impact of FTY720, a S1P receptor agonist, known to deplete lymphocytes from the peripheral blood by sequestering them into lymph nodes and Peyer's patches, on blood lymphocytes and graft infiltrating cells in a ra...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2016.01.003
更新日期：2016-03-01 00:00:00
abstract：:The outcome of hyperacute grade 3-4 steroid-refractory graft-versus-host-disease (SR-GVHD) remains dismal despite a plethora of agents being tried alone or in combination. Following T replete haploidentical transplantation with post-transplantation cyclophosphamide on 75 patients, 10 patients (13%) aged 2-20years, dev...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2016.08.009
更新日期：2016-11-01 00:00:00
abstract：OBJECTIVE:Acute rejection is a major cause of morbidity and mortality after solid organ transplantation. Therefore, optimizing treatment strategies and improving curative effect is urgent and necessary. Reliable biomarkers for acute rejection and the underlying molecular mechanisms remain to be determined. METHODS:In ...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2020.101320
更新日期：2020-10-01 00:00:00
abstract：:Over the last 25 years the importance of the humoral presensitization status of transplant recipients has increasingly been recognized. With greater understanding of the precise specificity of the pretransplant antibody status of recipients it is clear that the graft survival figures will improve. The development of n...
journal_title：Transplant immunology
pub_type： 杂志文章,评审
doi：10.1016/0966-3274(94)90045-0
更新日期：1994-06-01 00:00:00
abstract：:Alloreactivity probably involves T cell recognition of peptides bound to allogeneic HLA molecules. In order to study whether T cells recognizing common viral antigens presented by self HLA molecules also recognize some allogeneic HLA molecules we generated T lymphocyte clones (TLC) specific for herpes simplex virus (H...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/0966-3274(93)90005-s
更新日期：1993-01-01 00:00:00
abstract：BACKGROUND:Donor leucocytes (DL) play an important role in rat liver transplant tolerance and their postoperative administration can convert rejection to tolerance. They appear to induce early activation, altered patterns of infiltration and death of recipient alloreactive T cells. The ability of immunosuppressive drug...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2004.05.003
更新日期：2004-11-01 00:00:00
abstract：:Regulatory T cells, especially CD4(+)CD25(+) regulatory T cells are critical regulators of immune tolerance in humans and mice. Mice with humanized immunity have been developed by various transplantation strategies of human tissues or cells related to immunity, which are being extensively applied in biomedical researc...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2011.08.003
更新日期：2011-12-01 00:00:00
abstract：:We suggest that surveillance for squamous cell cancer might be particularly useful for transplant patients receiving statin therapy. We recommend that development of non melanoma skin cancer should be specified as a secondary endpoint in future large endpoint statin trials, and suggest that in transplant patients the ...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/j.trim.2010.06.001
更新日期：2010-08-01 00:00:00
abstract：:Tissue eosinophils have been previously implicated in allograft rejection and graft loss. The aim of this study was to evaluate the role of eosinophils in acute renal allograft rejection. Data from 71 patients with 114 renal biopsies with acute allograft rejection were compared with those from 26 controls. The median ...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/0966-3274(94)90076-0
更新日期：1994-01-01 00:00:00
abstract：:Although natural killer cells lyse targets without pre-sensitization, and in an MHC-unrestricted manner, they can also respond to healthy allogeneic cells of different MHC type. Such alloreactivity is a consequence of NK cells using clonally distributed, inhibitory MHC class I receptors to achieve tolerance to healthy...
journal_title：Transplant immunology
pub_type： 杂志文章,评审
doi：10.1016/j.trim.2006.09.022
更新日期：2006-12-01 00:00:00
abstract：:Introduction of MHC class I Kb cDNA via recombinant retrovirus into B10.AKM (Kk) bone marrow cells (BMC) has been shown to confer specific hyporesponsiveness to B10.MBR (Kb) allogeneic skin grafts in lethally irradiated B10.AKM recipients of the transduced syngeneic BMC. We have recently developed a nonmyeloablative c...
journal_title：Transplant immunology
pub_type： 杂志文章
doi：10.1016/s0966-3274(96)80044-x
更新日期：1996-03-01 00:00:00
