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 enterotoxin A (SEA)-mediated proliferation test. To evaluate their efficacy, the compounds were screened in a low-responder heart allograft transplantation model in rats [heart from Piebald Virol Glaxo (PVG) transplanted to Dark Agouti (DA)]. The immunosuppressive effects of the compounds were then investigated in a high-responder model (DA to PVG). Treatment with ABR-222417 (30 mg/kg) was more efficient than that with ABR-224050 (10 mg/kg), and the former provided a longer graft median survival time (MST, 29.5 days) than the latter (MST, 18.5 days). Furthermore, there was a marked increase in graft survival time (53 days) when low doses of ABR-222417 and cyclosporine A (CsA) were used in combination. No sign of tolerability problems was detected using this combination or when ABR-222417 was used singly at a higher dose. Furthermore, T-cell proliferation studies in vitro support that the anti proliferative effect of ABR-222417 is caused by inhibition of de novo pyrimidine synthesis, which is the consequence of DHODH inhibition. These results show that ABR-222417 had marked immunosuppressive effects on the heart allograft transplantation and that it exerts an even more powerful inhibitory effect on graft rejection when used in combination with CsA, with good tolerability.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Chen J,Xia J,Axelsson B,Fritzson I,Ekberg H,Törngren M,Qi Zdoi
10.1016/j.trim.2010.05.005subject
Has Abstractpub_date
2010-08-01 00:00:00pages
180-4issue
4eissn
0966-3274issn
1878-5492pii
S0966-3274(10)00070-5journal_volume
23pub_type
杂志文章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:Although high-mobility group box-1 (HMGB1), which is a nuclear protein, was reported to enhance the allogeneic responses in transplantation, the effect of HMGB1 on bronchiolitis obliterans syndrome (BOS) is unknown. METHODS:A murine heterotopic tracheal transplantation model was used. Protein concentrations...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.11.007
更新日期:2019-04-01 00:00:00
abstract::The immune system is an adaptive defense system capable of specifically recognizing and eliminating an apparently limitless variety of foreign invaders. This highly specific response is provided by T and B lymphocytes. The enormous diversity of the antigen-specific receptors on these cells is generated by random rearr...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/s0966-3274(02)00056-4
更新日期:2002-08-01 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::Adhesion molecule expression is an important event during early transplant failure. The aim of the present study was to examine the release of adhesion molecules during the first minutes of kidney allograft reperfusion in relation to delayed graft function and acute graft rejection. We enrolled 49 renal transplant rec...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.08.002
更新日期:2006-11-01 00:00:00
abstract::Humoral rejection and its relationship with anti HLA antibodies have been extensively studied in organ transplantation with the exception of liver transplantation (LT). Recently, association between donor specific anti HLA antibodies (DSA) and increased risk of rejection and graft loss has been suggested in LT. When s...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.01.007
更新日期:2016-03-01 00:00:00
abstract::Immunisation against Human Leucocyte Antigens (HLA) can be caused by pregnancy, blood transfusion, or organ transplants. The HLA antibody status of a given patient significantly influences their access and waiting time to transplant. For some highly sensitised patients (HSP) there is hardly any suitable donor availabl...
journal_title:Transplant immunology
pub_type: 社论
doi:10.1016/j.trim.2020.101354
更新日期:2021-02-01 00:00:00
abstract::Administration of anti-D immunoglobulin to D- women after delivery of a D+ infant has dramatically reduced the number of immunised women and cases of haemolytic disease of the fetus and newborn. The use of monoclonal anti-D might alleviate some of the pressures on maintaining adequate supplies of plasma sourced anti-D...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/s0966-3274(02)00066-7
更新日期:2002-08-01 00:00:00
abstract::Previously, we established a murine model, that involves the engraftment of fully allogeneic T cell depleted donor bone marrow cells in sublethally irradiated and single dose anti-CD3 treated recipient mice. These mice developed permanent stable multilineage mixed chimerism and donor-specific tolerance without graft-v...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/S0966-3274(02)00157-0
更新日期:2003-07-01 00:00:00
abstract:BACKGROUND:The potential of mesenchymal stem cells (MSCs) for immunosuppression has been tested in transplantation, but its mechanisms are not fully understood. This study investigated the role of MSC-expressing B7-H1 in the induction of immune tolerance to cardiac allografts by the combination therapy of MSCs and rapa...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2014.06.005
更新日期:2014-08-01 00:00:00
abstract::Adenoviral gene transfer is a potential ex vivo gene therapy for islet transplantation. However, the immunogenicity of adenoviral vectors can potentially impair vector efficacy in transplants where long-term gene expression is required. We investigated the effect of this antiviral immunity on vector expression and isl...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.02.001
更新日期:2009-05-01 00:00:00
abstract::The ImmuKnow assay measures cell-mediated immunity, quantifying ATP production from peripheral blood CD4+T-cells in solid-organ transplant patients who undergo immunosuppressive therapy. We aimed to measure functional immunity in lung transplant recipients and correlate Immuknow values with immunosuppression levels, p...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.04.001
更新日期:2016-07-01 00:00:00
abstract:BACKGROUND:The Fischer-to-Lewis (LEW) rat model of kidney transplantation is a widely accepted and well-characterized model of chronic rejection. In contrast to transplantation in a clinical setting, however, the absence of treatment with immunosuppressants and only minor mismatch of major histocompatibility complexes ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.08.002
更新日期:2016-09-01 00:00:00
abstract:OBJECTIVES:To assess the timelines of serum free light chain (sFLC) concentrations and the kappa/lambda light chain (K/L) ratio in heart transplant (HTX) recipients. To analyze the performance of serum protein electrophoresis (SPE), serum immunofixation (sIFE) and sFLC measurements for gammopathy detection following a ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2017.01.003
更新日期:2017-03-01 00:00:00
abstract::Chronic allograft dysfunction is one of the most important reasons for late graft loss after renal transplantation. Its etiology is multifactorial and combines immunological as well as non-immunological mechanisms. It is known from large registry data that MHC mismatches are inversely correlated to long term allograft...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.09.007
更新日期:2010-02-01 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::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::Calcineurin inhibitors (CNI) cyclosporine (Csa) and tacrolimus (Tac) are now first intention immunosuppressive drugs in renal transplantation. However, although these treatments are effective for preventing allograft rejection, they are nephrotoxic: they can cause chronic renal dysfunction and degradation of renal gra...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2008.09.002
更新日期:2008-11-01 00:00:00
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...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2019.101248
更新日期:2020-02-01 00:00:00
abstract::Solid organ transplant recipients (SOTRs) are susceptible to various cutaneous side effects as a consequence of long-term immunosuppressive therapy. Skin cancers and infections are well-studied complications that can cause death and/or allograft rejection. Other cutaneous drug reactions, such as inflammatory manifesta...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101355
更新日期:2021-02-01 00:00:00
abstract::A rapid and robust limiting dilution assay was developed to measure the frequency of donor-reactive, IL-2 (interleukin 2) producing, helper T lymphocytes in the peripheral T cell population of organ allograft recipients. The IL-2 bioassay was performed using two methodologies to assess the response of CTLL-2 indicator...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(94)90006-x
更新日期:1994-12-01 00:00:00
abstract::Desferrioxamine (DFO), commonly used in therapy as a chelator of ferric ion in disorders of iron overload, is a potent inhibitor of human cytomegalovirus (HCMV) replication in cultured fibroblast cells. Moreover, DFO has immunomodulatory activity both in vitro and in vivo. We studied DFO effects on HCMV replication in...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(95)80017-4
更新日期:1995-12-01 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::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::The expression of CD30 is restricted to cells of the immune system and strictly regulated under physiological conditions. However, active immune cells express CD30 and soluble CD30 (sCD30) is released. Several investigators reported the relevance for sCD30 as a predictive marker for allograft rejection following organ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2010.07.001
更新日期:2010-08-01 00:00:00
abstract::Recently, the signal transducer and activator of transcription 4 (STAT4) gene have been associated with multiple autoimmune diseases. Taking into consideration that the different autoimmune diseases may share some common pathogenetic pathways, the aim of the present study was to evaluate the role of STAT4 rs7574865 po...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.01.001
更新日期:2011-05-01 00:00:00
abstract::Mouse hearts transplanted into MHC disparate donors are usually rejected 1 week after placement. It is widely accepted that alloantigen-reactive helper T lymphocytes (HTL) and cytotoxic T lymphocytes (CTL) are the key mediators of acute allograft rejection. This report demonstrates that the presence or absence of 'tra...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(95)80028-x
更新日期:1995-09-01 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::Mixed lymphocyte reaction (MLR) assays were performed serially over 24 months in 19 first cadaver renal transplant recipients. Immunosuppression consisted of cyclosporine, methylprednisolone and azathioprine. Cyclosporine was withdrawn at 6 months postoperatively. The MLR reactivity gradually decreased over the first ...
journal_title:Transplant immunology
pub_type: 临床试验,杂志文章
doi:10.1016/s0966-3274(98)80016-6
更新日期:1998-12-01 00:00:00
abstract::We investigated the dynamics of the CD4+ and CD8+ lymphocyte subsets, and the expression of activation markers in cardiac transplant recipients. We tested 132 peripheral blood samples from 62 cardiac transplant recipients using fluorescent staining and flow cytometry analysis. The results were correlated with histolog...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(02)00072-2
更新日期:2002-11-01 00:00:00