Abstract:
:Persistent rejection in the face of treatment and multiple episodes of rejection are associated with the development of chronic rejection and graft loss in solid organ transplantation. The factors that create an environment for rejection that persists in the face of treatment are as yet not understood. The objective of this study was to evaluate the risk factors, including human multidrug resistance gene (MDR1), cytochrome P4503A5 (CYP3A5) and cytokine gene polymorphisms, associated with acute persistent rejection (APR) in lung transplant patients. One hundred and twenty-five adult lung transplant patients were studied. MDR1 G2677T, C3435T and CYP3A5 polymorphisms were assessed by direct sequencing of the polymorphic region in patient DNA. Cytokine genotyping for five cytokines was performed using the polymerase chain reaction-sequence specific primers (PCR-SSP) technique. Multivariate regression analysis was used to identify the predictors of acute persistent rejection. The dependent variable was the presence or absence of acute persistent rejection based on lung biopsies during the first postoperative year. The independent variables were MDR1 G2677T and C3435T, CYP4503A5 and cytokine polymorphisms, survival status, age, gender, survival days and HLA mismatches. The MDR1 C3435T polymorphism and age were independently associated with acute persistent rejection (p = 0.025, odds ratio = 0.29, 95% CI 0.1-0.86 and p = 0.016, odds ratio = 0.94, 95% CI 0.89-0.98, respectively). For the MDR1 C3435T polymorphism, 72% of patients with the C allele had acute persistent rejection in comparison to 52% for TT patients (p = 0.04). For age, a significant difference was found between the nonrejection group and the rejection group (mean+/-S.D. 52.1+/-11.2 vs. 44.4+/-12.3, p = 0.01). This is the first report of the association of a drug disposition genotype with drug-resistant acute rejection in organ transplant patients. The major predictor of acute persistent rejection in the first postoperative year for lung transplant patients was the MDR1 C3435T genotype. This association could be due to drug resistance, altered drug disposition or other immunologic effects associated with P-glycoprotein (P-gp) function. Future prospective treatment algorithms should be developed that will incorporate the knowledge of gene polymorphisms into treatment regimens to improve the outcome following lung transplantation.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Zheng HX,Zeevi A,McCurry K,Schuetz E,Webber S,Ristich J,Zhang J,Iacono A,Dauber J,McDade K,Zaldonis D,Lamba J,Burckart GJdoi
10.1016/j.trim.2004.11.001subject
Has Abstractpub_date
2005-03-01 00:00:00pages
37-42issue
1eissn
0966-3274issn
1878-5492pii
S0966-3274(04)00112-1journal_volume
14pub_type
杂志文章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::In this review, we summarize the work published over the last few years relative to cellular immunological hurdles encountered specifically in pig-to-primate xenotransplantation models. The works summarized here cover both the innate and adaptative cellular immune response as well as strategies to overcome them and co...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2008.10.006
更新日期:2009-06-01 00:00:00
abstract::There have been several reports that xeno-MHC-restricted T-cells have a cytotoxic function through a direct xenoantigen recognition, but yet no report that they have a helper function. Previously we showed that both xeno-MHC-restricted CD4(+) and CD8(+) T-cells recognized xenoantigens directly in a mouse anti-rat comb...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/S0966-3274(02)00158-2
更新日期:2003-04-01 00:00:00
abstract::Allospecific memory T cells are a recognized threat to the maintenance of solid-organ transplants. Limited information exists regarding the development of alloreactive memory T cells when post-transplant immunosuppression is present. The clinical practice of delaying calcineurin inhibitor (CNI) initiation post-transpl...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2014.10.001
更新日期:2015-01-01 00:00:00
abstract::Naturally occurring antibodies to the galactose alpha1,3 galactose (alpha gal) epitope expressed on xenogeneic grafts are a major barrier to organ transplantation in humans. Porcine small intestinal submucosa (SIS) expresses the alpha gal epitope and is currently being used as a bioscaffold for tissue remodeling. To e...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(01)00044-2
更新日期:2002-06-01 00:00:00
abstract::TCR-beta (T cell receptor-beta chain) transgenic mice have altered lymphocyte development. TCR-beta transgenic mice are hyporesponsive to alloantigens in vivo and are deficient in gamma delta T cells. In order to begin a study of the relationship between a deficiency of alloreactive gamma delta cells and the defective...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(94)90063-9
更新日期:1994-09-01 00:00:00
abstract:BACKGROUND:Mesenchymal stem cells (MSCs) can be used for immunomodulation therapy after solid organ transplantation. Here, we focus on the immunoregulatory potential of combination therapies of MSCs and classic pharmacotherapy to mediate acceptance of solid organ grafts. METHODS:To determine which drugs influence the ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.06.002
更新日期:2011-09-01 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: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::Induction of donor-specific hyporesponsiveness would minimize the need for intensive immunosuppression in the clinical setting of graft rejection and dendritic cells (DCs) might be useful tools for this purpose. Besides their ability to induce immunogenic T-cell responses, these antigen presenting cells can lead to T-...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.03.001
更新日期:2006-06-01 00:00:00
abstract::Models of severe combined immuno-deficient (SCID) mice reconstituted with a competent human immune system represent a valuable tool for the study of human immune responses in vivo. Reconstitution with human cells can be achieved using large numbers of peripheral blood lymphocytes, but levels of engraftment are poor an...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2005.07.002
更新日期:2005-12-01 00:00:00
abstract::Previously, we developed a well-tolerated single-day protocol for induction of stable multilineage chimerism and permanent donor-specific tolerance across major histocompatibility complex (MHC) barriers, with preservation of the host's normal immune responses. In our murine model, recipient mice were treated with a si...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(98)80039-7
更新日期:1998-09-01 00:00:00
abstract:INTRODUCTION:Destruction of transplanted kidneys through chronic allograft nephropathy [CAN], also known as chronic rejection, is the greatest obstacle in successful kidney transplantation. Causes behind CAN are many, from pre-transplant causes to infections. Viral infections, especially CMV, are a risk factor for chro...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2007.07.004
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:We tested the hypothesis that the best time for genetic modification is while the cell viability of the graft is reduced for long-term preservation. The hemagglutinating virus of Japan (HVJ)-liposome method, a nonviral gene transfer technique, was used with a luciferase gene to test the efficacy of protein i...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/S0966-3274(03)00002-9
更新日期:2003-01-01 00:00:00
abstract::The aetiologies of accelerated or transplant-associated coronary artery disease (TxCAD) following cardiac transplantation and chronic rejection following renal transplantation remain ill-defined. Previous studies have used Western blotting to demonstrate an association between the formation of anti-endothelial (anti-E...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(97)80021-4
更新日期:1997-03-01 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::Complex polygenic and multifactorial diseases remain a challenge for human geneticists. Here we aim to remind basic definitions of multifactorial diseases and the genetic related concepts underlying classical methods. Knowledge on pathophysiological process and the genetic information available conditions the design o...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2005.03.015
更新日期:2005-08-01 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::Using specific cell surface receptors lymphocytes continuously sample their environment. Maturation of the immune system and initiation of a specific immune response rely on an array of extracellular cues that elicit complex intracellular biochemical signals. Essential molecules involved in signal transduction from im...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/s0966-3274(02)00009-6
更新日期:2002-05-01 00:00:00
abstract:OBJECTIVE:To investigate the expression and significance of Sirt1 in renal allografts at the early stage of chronic renal allograft dysfunction (CRAD). METHODS:CRAD rat models were established using classical orthotopic F344-Lewis kidney transplantation. F344 and Lewis uninephrectomized rats were used as controls. Twe...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.02.006
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:Conditioning chemotherapies for hematopoietic stem cell transplantation (HSCT), especially those that include total body irradiation, can result in serious complications such as graft-versus-host disease (GVHD). Human leukocyte antigen G (HLA-G) is a non-classical class I molecule with multiple immunoregulat...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.12.001
更新日期:2019-04-01 00:00:00
abstract::TIRC7 delivers essential signals during immune activation as antibodies targeting TIRC7 inhibit lymphocyte proliferation and Th1 cytokine expression in vitro and prolonged kidney and heart allograft survival in vivo. Immunohistochemical analysis of biopsy specimens from human renal allografts undergoing rejection desp...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.09.027
更新日期:2006-11-01 00:00:00
abstract::B(io) B(reedding)/O(ttawa) K(alsburg) rats spontaneously develop insulin-dependent type 1 diabetes. Days before BB/OK rats become diabetic, their body seems to be flabby which may be attributed to loss of subcutaneous fat. However, the rats are normoglycemic and manifest 3-4 days later. This observation prompted us to...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.01.003
更新日期:2011-05-01 00:00:00
abstract::Organ transplantation is an effective way to treat many end-stage diseases. In order to overcome post-transplant rejection, immunosuppressive agents have been widely used, but the long-term survival of transplanted organs still has not been achieved in the clinic. For decades, tolerance is the "holy grail" that transp...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2019.101250
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:The complexity of surgical procedure in mouse heterotopic heart transplantation (HHT) has prevented its widespread use. The present study reported a modified technique - splint tubing technique (STT) based on cuff technique (CT). MATERIALS AND METHODS:C57BL/10 and BALB/c mice were performed in syngeneic and...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.03.005
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND:After lung transplantation, the major complication limiting the long-term survival of allografts is obliterative bronchiolitis (OB), characterized by chronic rejection. Innate immune responses contribute to the development of OB. In this study, we used a murine heterotopic tracheal transplantation mouse mode...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.11.006
更新日期:2019-04-01 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: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::MicroRNAs are small, noncoding RNAs that control expression of target genes through inhibiting protein translation or inducing degradation of mRNA transcripts of target genes. According to the latest update, 2578 unique mature miRNAs are currently annotated in the human genome and participate in the regulation of mult...
journal_title:Transplant immunology
pub_type: 临床试验,杂志文章
doi:10.1016/j.trim.2017.06.002
更新日期:2017-08-01 00:00:00
abstract::Application of mesenchymal stromal cells (MSCs) has been proposed for solid organ transplantation based on their potent immuno-modulatory effects in vitro and in vivo. We investigated the potential of MSCs to improve acceptance of kidney transplants in an MHC-incompatible rat model including isogeneic kidney transplan...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2013.08.004
更新日期:2013-12-01 00:00:00