Abstract:
:The success of kidney transplants is limited by the lack of robust improvements in long-term survival. It is now recognized that alloimmune responses are responsible for the majority of allograft failures. Development of novel therapies to decrease allosensitization is critical. The lack of new drug development in kidney transplantation necessitated repurposing drugs initially developed in oncology and autoimmunity. Among these is tocilizumab (anti-IL-6 receptor [IL-6R]) which holds promise for modulating multiple immune pathways responsible for allograft injury and loss. Interleukin-6 is a cytokine critical to proinflammatory and immune regulatory cascades. Emerging data have identified important roles for IL-6 in innate immune responses and adaptive immunity. Excessive IL-6 production is associated with activation of T-helper 17 cell and inhibition of regulatory T cell with attendant inflammation. Plasmablast production of IL-6 is critical for initiation of T follicular helper cells and production of high-affinity IgG. Tocilizumab is the first-in-class drug developed to treat diseases mediated by IL-6. Data are emerging from animal and human studies indicating a critical role for IL-6 in mediation of cell-mediated rejection, antibody-mediated rejection, and chronic allograft vasculopathy. This suggests that anti-IL-6/IL-6R blockade could be effective in modifying T- and B-cell responses to allografts. Initial data from our group suggest anti-IL-6R therapy is of value in desensitization and prevention and treatment of antibody-mediated rejection. In addition, human trials have shown benefits in treatment of graft versus host disease in matched or mismatched stem cell transplants. Here, we explore the biology of IL-6/IL-6R interactions and the evidence for an important role of IL-6 in mediating allograft rejection.
journal_name
Transplantationjournal_title
Transplantationauthors
Jordan SC,Choi J,Kim I,Wu G,Toyoda M,Shin B,Vo Adoi
10.1097/TP.0000000000001452subject
Has Abstractpub_date
2017-01-01 00:00:00pages
32-44issue
1eissn
0041-1337issn
1534-6080journal_volume
101pub_type
杂志文章,评审相关文献
TRANSPLANTATION文献大全abstract:BACKGROUND:In a recent trial, targeted mild hypothermia in brain-dead organ donors significantly reduced the incidence of delayed graft function after kidney transplantation. This trial was stopped early for efficacy. Here, we report long-term graft survival for all organs along with donor critical care end points. ME...
journal_title:Transplantation
pub_type: 杂志文章,随机对照试验
doi:10.1097/TP.0000000000002890
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND:The full potential of pancreatic islet transplantation (PIT) has not been realized because of the difficulties associated with islet isolation, particularly when associated with a remote islet isolation center. Herein, we describe the principles of pancreatic procurement for PIT, which have allowed us to ach...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000128910.41921.4b
更新日期:2004-08-15 00:00:00
abstract::Glutathione and glyoxalase II levels were evaluated in cytosolic and mitochondrial compartments of rat liver after 7 and 24 hr of cold storage in University of Wisconsin (UW) and Euro-Collins solutions. 1-4 A similar time-dependent depletion of cytosolic glutathione up to about 60% of control values was observed in bo...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199605150-00026
更新日期:1996-05-15 00:00:00
abstract:BACKGROUND:Because CD4CD25Foxp3 regulatory T cells (Tregs) are essential for the maintenance of self-tolerance, significant interest surrounds the developmental cues for thymic-derived natural Tregs (nTregs) and periphery-generated adaptive Tregs (aTregs). In the transplant setting, the allograft may play a role in the...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e31820e50b3
更新日期:2011-04-15 00:00:00
abstract::Cyclosporine prevents the development of diabetes in spontaneously diabetic BB rats and NOD mice. However, islet transplants have been shown to be subject to immunologic destruction in hosts treated with CsA and anti-CD4 antibody or those rendered tolerant to donor antigens. This study determines whether the minimum d...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199005000-00001
更新日期:1990-05-01 00:00:00
abstract:BACKGROUND:The timing of an acute rejection may have a variable impact on renal allograft survival. To determine whether the time of first acute transplant rejection (ATR) is an independent predictor of long-term allograft survival, we studied 31,600 first cadaveric renal transplants that were functional on the first t...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199705150-00013
更新日期:1997-05-15 00:00:00
abstract:BACKGROUND:Transplant vasculopathy in kidney and heart allografts is associated with marked elevation of endothelin-1 (ET-1), but a role for ET-1 in the pathogenesis of transplant vasculopathy and chronic rejection has not been established. We, therefore, tested whether inhibition of ET-1-converting enzyme by phosphora...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199906270-00007
更新日期:1999-06-27 00:00:00
abstract::Rapid and precise cyclosporine measurements are necessary to maximize immunosuppression and minimize toxicity. The new cyclosporine and metabolites TDx fluorescent polarization immunoassay was studied to determine its precision, sensitivity, and stability. Further, it was compared with the existing radioimmunoassay an...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198902000-00013
更新日期:1989-02-01 00:00:00
abstract::The presence of major histocompatibility complex (MHC)-encoded antigens (RT1) on endothelium of rat kidneys was investigated using hyperimmune allogeneic rat sera (HIS) in an indirect immunofluorescence technique with kidney sections. Endothelial antigens detected with anti-MHC sera segregated in an F2 generation with...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198209000-00002
更新日期:1982-09-01 00:00:00
abstract:INTRODUCTION:This is a follow-up of a withdrawal study that we previously performed on 104 liver transplant patients in which immunosuppression was gradually withdrawn over a period of 3 years. Eighty-one patients were not able to be withdrawn (rejectors), and 23 patients were successfully weaned off immunosuppression ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3182003db7
更新日期:2010-12-27 00:00:00
abstract:BACKGROUND:This study is designed to examine a possible association of cardiopulmonary bypass (CPB) support and outcome of lung transplantation in a well-balanced group of emphysema patients. METHODS:We performed a retrospective analysis of 62 consecutive primary bilateral lung transplantations for emphysema. Risk fac...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200205270-00017
更新日期:2002-05-27 00:00:00
abstract::In three patients with end-stage renal failure due to primary hyperoxaluria type 1, successful combined liver-kidney transplantation enabled us to assess the insoluble oxalate pool, which was compared with the histopathological changes observed in iliac crest biopsy specimens. Good correlation was observed between the...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199506270-00010
更新日期:1995-06-27 00:00:00
abstract::Intestinal transplantation has become the treatment of choice for patients who are experiencing life-threatening complications of intestinal failure. Early attempts with intestinal transplantation were unsuccessful as a consequence of both technical and immunologic failures. The introduction of tacrolimus provided the...
journal_title:Transplantation
pub_type: 杂志文章,评审
doi:10.1097/01.tp.0000126931.23349.15
更新日期:2004-05-15 00:00:00
abstract:BACKGROUND:Infectious diseases are a major source of morbidity and mortality for immunosuppressed transplant recipients and the antimicrobial chemotherapy can be often less effective in these individuals, because the contribution of underlying host defenses is absent. METHODS:The influence of co-amoxiclav on the funct...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200102270-00016
更新日期:2001-02-27 00:00:00
abstract::ICAM-1 is an inducible glycoprotein important in the adhesion, activation, and transmigration of circulating leukocytes across the vascular endothelial monolayer, and it likely plays a key role in the allogeneic response. To determine the reproducibility and significance of variations in resting levels of cell surface...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199410270-00015
更新日期:1994-10-27 00:00:00
abstract:BACKGROUND:Delayed graft function (DGF) is associated with acute tubular necrosis. In this setting, surviving tubular cells may proliferate and replace injured cells. CD133Pax-2cells may play a role in the regeneration of tubular damage. The aim of this study was to demonstrate the presence of these cells in human kidn...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e31816a8891
更新日期:2008-04-27 00:00:00
abstract:BACKGROUND:Galbeta1-4GlcNAcalpha2-6 sialyltransferase (ST6GalI) is an acute phase reactant whose release from cells can be induced by proinflammatory cytokines. Because patients with chronic renal failure have high circulating levels of proinflammatory cytokines, we hypothesized that patients on the renal transplant wa...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200003150-00022
更新日期:2000-03-15 00:00:00
abstract::A 22-year-old previously nonsensitized female patient (HLA-A2,28; B7,14; DR1,2) received a kidney from her HLA-identical brother. She irreversibly rejected the graft 2 1/2 weeks later. In vitro tests performed 6 weeks after the graft loss, using recipient responding and donor-stimulating and target cells, revealed a w...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198201000-00011
更新日期:1982-01-01 00:00:00
abstract::Second clinical kidney grafts often survive longer than first grafts. Using a rat cardiac allograft model, we examined the conditions under which survival of a second graft can be longer than first graft survival. In the BUF-to-LEW combination, following rejection of the first transplant, second cardiac allografts fro...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199210000-00025
更新日期:1992-10-01 00:00:00
abstract::The histopathological changes and the course of graft-versus-host (GVH) disease were studied in the rat model of small-bowel transplantation using the Lewis----LBN-F1 strain combination. Allograft-induced GVH disease led to the recipients' death from enteritis, dermatitis and emaciation after 14.4 +/- 2.9 days (hetero...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198603000-00002
更新日期:1986-03-01 00:00:00
abstract:BACKGROUND:Bioluminescence imaging (BLI) modalities are being developed to monitor islet transplant mass and function in vivo. The aim of this study was to use the BLI system to determine how the change in functional islet mass correlated to metabolic abnormalities during the course of alloimmune rejection in a murine ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000206109.71181.bf
更新日期:2006-05-27 00:00:00
abstract::Nonmajor histocompatibility complex (non-MHC) antigens are important targets of graft rejection and graft-versus-host disease in clinical transplantation. Little is known regarding immunity to non-MHC antigens. To study this problem we evaluated the effect of antihuman thymocyte globulin (ATG) on reactivity in autolog...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198102000-00001
更新日期:1981-02-01 00:00:00
abstract:BACKGROUND:Mixed allogeneic bone marrow chimerism induces tolerance to solid organ grafts. Although we previously reported that partially ablative conditioning with 700 cGy of total body irradiation (TBI) is sufficient to allow for bone marrow engraftment in mice, we determined that a minimum of 1000 cGy was required i...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199908150-00008
更新日期:1999-08-15 00:00:00
abstract:BACKGROUND:In clinical transplantation, "passenger" dendritic cells (DCs) in the allograft have been thought to induce allograft rejection. However, the presence of DCs in the normal human kidney is controversial. Most reports have relied on the examination of MHC class I and II antigen expression in combination with D...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199804150-00025
更新日期:1998-04-15 00:00:00
abstract:OBJECTIVE:Exact knowledge of biliary anatomy is essential in living donor liver transplantation. The purpose of this study was to evaluate the accuracy of pretransplant magnetic resonance cholangiography (MRC) in depicting the biliary anatomy in comparison with intraoperative cholangiography (IOC). MATERIALS AND METHO...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e31821c1e33
更新日期:2011-07-15 00:00:00
abstract::We developed a hepatic arterialization technique in living donor liver transplantation. The technique was indicated in patients with a left graft from donors with a right hepatic artery originated from superior mesenteric artery or a right graft from donors with a left hepatic artery from left gastric artery. The dono...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000236102.36326.a6
更新日期:2006-12-15 00:00:00
abstract:BACKGROUND:The aim of our study was to examine, in a recent cohort of kidney transplant recipients who have received modern immunosuppressive therapy, the respective role of cold ischemia time (CIT) and delayed graft function (DGF) on acute rejection (AR) rates and long-term graft survival. METHODS:We retrospectively ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e318169c29e
更新日期:2008-04-15 00:00:00
abstract::To examine whether cyclosporine (CsA) has mutagenic potential against human cells, we analyzed sister chromatid exchange (SCE) induction by CsA using human lymphocytes in vitro. SCE frequencies increased significantly in the lymphocytes treated with 1 microgram/ml and 5 micrograms/ml CsA, though the frequencies seemed...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1986-07-01 00:00:00
abstract::Rat, hamster, and rabbit islets were transplanted into diabetic C57BL/B6 mice. The effect on islet xenograft survival of low-temperature culture of the donor islets, alpha L3T4 treatment of the recipients for seven days, and transplantation of the grafts either in the renal capsule or in the liver via the portal vein ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198905000-00002
更新日期:1989-05-01 00:00:00
abstract::An increased frequency of kidney rejection has been reported in diabetic patients who have simultaneous pancreas and kidney transplantation compared with patients who have a kidney transplant alone. Kidney graft outcome is similar in the two groups. The mechanism for increased kidney graft rejection with a simultaneou...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199304000-00015
更新日期:1993-04-01 00:00:00