Journal ArticleAm J Transplant · October 22, 2025
Antibody-mediated rejection (AMR) remains a significant barrier to successful outcomes in both allo- and xenotransplantation. In this study, we investigate the efficacy of a novel recombinant endopeptidase, IceMG, which simultaneously cleaves IgG and IgM i ...
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Journal ArticleSci Adv · September 5, 2025
Antibody-mediated rejection is a leading cause of allograft failure and mortality in pediatric solid organ transplant recipients. Current apheresis systems require large blood volumes and are primarily designed for adults, making them unsuitable for childr ...
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Journal ArticleBlood · August 28, 2025
Rapid CD137 upregulation on alloreactive T cells upon allogeneic stimulation suggests that their selective elimination could prevent acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HCT). Here, we developed ...
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Journal ArticleSci Transl Med · January 2025
Current desensitization and maintenance immunosuppression regimens for kidney transplantation in sensitized individuals show limited ability to control the posttransplant humoral response, resulting in high rates of antibody-mediated rejection (ABMR) and g ...
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Journal ArticleXenotransplantation · 2025
BACKGROUND: The removal of preformed antibodies with cleaving enzyme like IdeS (Imlifidase) has demonstrated therapeutic potential in organ transplantation for sensitized recipients. However, preformed xenoreactive antibodies (XAbs) against porcine glycans ...
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Journal ArticleXenotransplantation · 2025
BACKGROUND: The removal of preformed antibodies with cleaving enzymes like IdeS (imlifidase) has demonstrated therapeutic potential in organ transplantation for sensitized recipients. However, preformed xenoreactive antibodies (XAbs) against porcine glycan ...
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Journal ArticleXenotransplantation · 2025
BACKGROUND: Surgical bleeding is a risk in any solid organ transplant, and is commonly addressed with the transfusion of human blood products to replace or supplement coagulation factors. It is unknown if these blood products would harm xenotransplanted pi ...
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Journal ArticleTransplant Proc · 2025
BACKGROUND: Skin transplantation is often used in nonhuman primate (NHP) transplant research for sensitization and to assess tolerance. However, the availability of donor animals for skin can be constrained after organ donation. In this study, we evaluated ...
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Journal ArticleNat Commun · August 10, 2024
Therapeutic apheresis aims to selectively remove pathogenic substances, such as antibodies that trigger various symptoms and diseases. Unfortunately, current apheresis devices cannot handle small blood volumes in infants or small animals, hindering the tes ...
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Journal ArticleHLA · July 2024
Xenotransplantation is a potential option for individuals for whom an acceptable human allograft is unavailable. Individuals with broadly reactive HLA antibodies due to prior exposure to foreign HLA are potential candidates for a clinical xenotransplant tr ...
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Journal ArticleImmunohorizons · July 1, 2024
The critical importance of the thymus for generating new naive T cells that protect against novel infections and are tolerant to self-antigens has led to a recent revival of interest in monitoring thymic function in species other than humans and mice. Nonh ...
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Journal ArticleSci Transl Med · June 12, 2024
Genetic modification of porcine donors, combined with optimized immunosuppression, has been shown to improve outcomes of experimental xenotransplant. However, little is known about outcomes in sensitized recipients, a population that could potentially bene ...
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Journal ArticleKidney Int · May 2024
Because of the global shortage of donor kidneys, xenotransplantation emerges as a potential solution for individuals with kidney failure who face challenges in securing a suitable donor kidney. A study featured in this month's issue of Kidney International ...
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ConferenceJCI Insight · March 8, 2024
Innate immune cells are important in the initiation and potentiation of alloimmunity in transplantation. Immediately upon organ anastomosis and reperfusion, recipient monocytes enter the graft from circulation and differentiate to inflammatory macrophages ...
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Journal ArticleXenotransplantation · 2024
BACKGROUND: Highly sensitized patients face many barriers to kidney transplantation, including higher rates of antibody-mediated rejection after HLA-incompatible transplant. IdeS, an endopeptidase that cleaves IgG nonspecifically, has been trialed as desen ...
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Journal ArticleMicrosyst Nanoeng · 2024
Separating plasma from whole blood is an important sample processing technique required for fundamental biomedical research, medical diagnostics, and therapeutic applications. Traditional protocols for plasma isolation require multiple centrifugation steps ...
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Journal ArticleXenotransplantation · 2024
This report summarizes the content of a debate sponsored by eGenesis Bio, organized by the International Xenotransplantation Association (IXA), and attended by more than 150 delegates in the context of the IPITA-IXA-CTRMS Joint Congress held in San Diego i ...
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Journal ArticleFront Transplant · 2024
OBJECTIVE: Cardiac Allograft Vasculopathy (CAV), a process of vascular damage accelerated by antibody-mediated rejection (AMR), is one of the leading causes of cardiac transplant failure. Proteasome inhibitors (PIs) are utilized to treat AMR, however PI-as ...
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Journal ArticleNature · October 2023
Recent human decedent model studies1,2 and compassionate xenograft use3 have explored the promise of porcine organs for human transplantation. To proceed to human studies, a clinically ready porcine donor must be engineered and its xenograft successfully t ...
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Journal ArticleSci Adv · May 19, 2023
Among sensitized patients awaiting a transplant, females are disproportionately represented, partly because of pregnancy-induced sensitization. Using female NHPs sensitized by pregnancy alone, we examined the efficacy of costimulation blockade and proteaso ...
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Journal ArticleAm J Kidney Dis · May 2023
There is growing interest in daratumumab in the solid organ transplant realm owing to the potential immunomodulatory effects on CD38-expressing cells, primarily plasma cells, as they have a key role in antibody production. In particular there is interest i ...
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Journal ArticleFront Transplant · 2023
INTRODUCTION: One-third of HLA-incompatible kidney transplant recipients experience antibody mediated rejection (AMR) with limited treatment options. This study describes a novel treatment strategy for AMR consisting of proteasome inhibition and costimulat ...
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Journal ArticleFront Transplant · 2023
Using novel drugs targeting lymphocyte costimulation, cytokines, antibody, complement, and plasma cells, we have developed strategies in a non-human primate model to modulate the B cell response to incompatible kidney transplants. After more than two decad ...
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Journal ArticleKidney360 · December 29, 2022
Preexisting donor-specific antibodies (DSA) to MHC antigens increase the risk of antibody-mediated rejection (AMR) in sensitized transplant recipients and reduces graft survival. Pretransplant desensitization with costimulation blockade and proteasome inhi ...
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Journal ArticleJ Immunol Methods · December 2022
BACKGROUND: Given the role of B cells in sensitization and antibody-mediated rejection pathogenesis, the ability to identify, isolate, and study B cells in vitro is critical for understanding these processes and developing novel therapeutics. While in vivo ...
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Journal ArticleAm J Transplant · December 2022
Sensitized patients, those who had prior exposure to foreign human leukocyte antigens, are transplanted at lower rates due to challenges in finding suitable organs. Desensitization strategies have permitted highly sensitized patients to undergo kidney tran ...
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Journal ArticleJ Am Soc Nephrol · October 2022
BACKGROUND: In kidney transplantation, early allograft inflammation impairs long-term allograft function. However, precise mediators of early kidney allograft inflammation are unclear, making it challenging to design therapeutic interventions. METHODS: We ...
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Journal ArticleJ Allergy Clin Immunol · September 2022
Establishing tolerance remains a central, if elusive, goal of transplantation. In solid-organ transplantation, one strategy for inducing tolerance has been cotransplantation of various forms of thymic tissue along with another organ. As one of the biologic ...
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Journal ArticleFront Immunol · 2022
Despite dramatic improvement in kidney transplantation outcomes over the last decades due to advent of modern immunosuppressive agents, long-term outcomes remain poor. Antibody-mediated rejection (ABMR), a B cell driven process, accounts for the majority o ...
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Journal ArticleFront Immunol · 2022
Aberrant activation of the complement system contributes to solid-organ graft dysfunction and failure. In kidney transplantation, the complement system is implicated in the pathogenesis of antibody- and cell-mediated rejection, ischemia-reperfusion injury, ...
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Journal ArticleCommun Biol · November 25, 2021
Multiplex immunoassays with acellular antigens are well-established based on solid-phase platforms such as the Luminex® technology. Cell barcoding by amine-reactive fluorescent dyes enables analogous cell-based multiplex assays, but requires multiple label ...
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Journal ArticleNat Commun · September 15, 2021
Sensitized kidney transplant recipients experience high rates of antibody-mediated rejection due to the presence of donor-specific antibodies and immunologic memory. Here we show that transient peri-transplant treatment with the central complement componen ...
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Journal ArticleJ Biomed Opt · September 2021
SIGNIFICANCE: The current gold standard for monitoring small intestinal transplant (IT) rejection is endoscopic visual assessment and biopsy of suspicious lesions; however, these lesions are only superficially visualized by endoscopy. Invasive biopsies pro ...
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Journal ArticleJ Clin Med · August 18, 2021
Patients with previous sensitization events against anti-human leukocyte antigens (HLA) often have circulating anti-HLA antibodies. Following organ transplantation, sensitized patients have higher rates of antibody-mediated rejection (AMR) compared to thos ...
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Journal Article · May 21, 2021
AbstractWe describe generation of stable, fluorescence-barcoded cell lines suitable for multiplex screening of antibody to membrane proteins. The utility of this cell-based system, capable of a 256-plex cell panel, is demonstrate ...
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Journal ArticleKidney Int · January 2021
Sensitized patients are difficult to transplant due to pre-formed anti-donor immunity. We have previously reported successful desensitization using carfilzomib and belatacept in a non-human primate (NHP) model. Here we evaluated selective blockade of the c ...
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Journal ArticleFront Immunol · 2021
BACKGROUND: In transplantation, plasmapheresis and IVIg provide the mainstay of treatment directed at reducing or removing circulating donor-specific antibody (DSA), yet both have limitations. We sought to test the efficacy of targeting the IgG recycling m ...
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Journal ArticleFront Immunol · 2021
There is an urgent need for therapeutic interventions for desensitization and antibody-mediated rejection (AMR) in sensitized patients with preformed or de novo donor-specific HLA antibodies (DSA). The risk of AMR and allograft loss in sensitized patients ...
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Journal ArticleFront Immunol · 2021
Antibody-mediated allograft rejection (AMR) causes more kidney transplant failure than any other single cause. AMR is mediated by antibodies recognizing antigens expressed by the graft, and antibodies generated against major histocompatibility complex (MHC ...
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Journal ArticleJCI Insight · October 15, 2020
Myeloid cells are increasingly recognized as major players in transplant rejection. Here, we used a murine kidney transplantation model and single cell transcriptomics to dissect the contribution of myeloid cell subsets and their potential signaling pathwa ...
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Journal ArticleTranspl Int · October 2020
Vascularized composite allotransplantation (VCA) is challenged by the morbidity of immunosuppression required to prevent rejection. The use of highly specific biologics has not been well explored in VCA. Given that psoriasis is T-cell mediated, as is rejec ...
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Journal ArticleAm J Transplant · October 2020
Allosensitization constitutes a major barrier in transplantation. Preexisting donor-reactive memory T and B cells and preformed donor-specific antibodies (DSAs) have all been implicated in accelerated allograft rejection in sensitized recipients. Here, we ...
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Journal ArticleSci Rep · July 17, 2020
The cellular mechanisms underlying impaired function of aged liver grafts have not been fully elucidated, but mitochondrial dysfunction appears to be contributory. Sirtuin1 has been identified as a key mediator of mitochondrial recovery following ischemia- ...
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Journal ArticleJCI Insight · June 4, 2020
Eighty-six infants born without a thymus have been treated with allogeneic cultured thymus tissue implantation (CTTI). These infants, who lack T cells and are profoundly immunodeficient at birth, after CTTI from an unmatched donor develop T cells similar t ...
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Journal ArticleAm J Transplant · June 2020
During the past 5 decades, short-term outcomes in kidney transplant have significantly improved, in large part due to reduced rates and severity of acute rejection. Development of better immunosuppressive maintenance agents, as well as new induction therap ...
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Journal ArticleTransplantation · May 2020
BACKGROUND: Calcineurin inhibitors successfully control rejection of transplanted organs but also cause nephrotoxicity. This study, using a rhesus monkey renal transplantation model, sought to determine the applicability of a new immunomodulatory drug inhi ...
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Journal ArticleTranspl Int · January 2020
Our understanding of the role of B cells in organ transplantation remains incomplete and continues to grow. The majority of research has focused on the detrimental role of antibodies that drive the development of pathogenesis of the transplanted organ. How ...
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Chapter · January 1, 2020
Antibody-mediated rejection (AMR) is a barrier to successful long-term xenograft survival. We compared AMR in kidney xenotransplantation to sensitized kidney allotransplantation in a nonhuman primate model. With conventional CNI-based immunosuppressive mai ...
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Journal ArticleJ Am Soc Nephrol · December 2019
BACKGROUND: Patients with broad HLA sensitization have poor access to donor organs, high mortality while waiting for kidney transplant, and inferior graft survival. Although desensitization strategies permit transplantation via lowering of donor-specific a ...
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Journal ArticleJCI Insight · August 22, 2019
Multiple organ failure (MOF) is the leading cause of late mortality and morbidity in patients who are admitted to intensive care units (ICUs). However, there is an epidemiologic discrepancy in the mechanism of underlying immunologic derangement dependent o ...
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Journal ArticleCurr Opin Organ Transplant · August 2019
PURPOSE OF REVIEW: Manipulating costimulatory signals has been shown to alter T cell responses and prolong graft survival in solid organ transplantation. Our understanding of and ability to target various costimulation pathways continues to evolve. RECENT ...
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Journal ArticleTransplant Rev (Orlando) · July 2019
Research in transplant immunology using non-human primate (NHP) species to evaluate immunologic strategies to prevent rejection and prolong allograft survival has yielded results that have translated successfully into human organ transplant patient managem ...
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Journal ArticleJ Am Soc Nephrol · July 2019
BACKGROUND: Donor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. Therefore, reducing the risk of these antibodies remains a clinical need in transplantation. Plasma cells are a logica ...
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Journal ArticleLiver Transpl · April 2019
Machine preservation (MP) has emerged as a promising technology in liver transplantation, but the cellular processes occurring during MP have not been characterized. Recent studies have noted the presence of inflammatory molecules generated during MP. We h ...
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Journal ArticleAm J Transplant · March 2019
Previous evidence suggests that a homeostatic germinal center (GC) response may limit bortezomib desensitization therapy. We evaluated the combination of costimulation blockade with bortezomib in a sensitized non-human primate kidney transplant model. Sens ...
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Journal ArticleLab Chip · January 29, 2019
Platelet separation is a crucial step for both blood donation and treatment of essential thrombocytosis. Here we present an acoustofluidic device that is capable of performing high-throughput, biocompatible platelet separation using sound waves. The device ...
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Journal ArticleTransplantation · August 2018
The purpose of this review is to discuss immunologic tolerance as it applies to solid organ transplantation and to identify barriers that hinder the achievement of this long-term goal. First, the definition of tolerance and an introduction of mechanisms by ...
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Journal ArticleTransplant Rev (Orlando) · July 2018
Thrombotic microangiopathy (TMA) is a histological feature of antibody-mediated rejection and has the potential to cause problematic graft dysfunction, particularly for highly sensitized cross-match positive kidney transplant recipients. Prompt recognition ...
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Journal ArticleFront Immunol · 2018
Despite significant improvements in injury prevention and emergency response, injury-related death and morbidity continues to increase in the US and worldwide. Patients with trauma, invasive operations, anti-cancer treatment, and organ transplantation prod ...
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Journal ArticleFront Immunol · 2018
Despite its excellent efficacy in controlling T cell mediated acute rejection, lymphocyte depletion may promote a humoral response. While T cell repopulation after depletion has been evaluated in many aspects, the B cell response has not been fully elucida ...
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Journal ArticleBlood Adv · November 14, 2017
Featured Publication
The detrimental effects of donor-directed antibodies in sensitized transplant patients remain a difficult immunologic barrier to successful organ transplantation. Antibody removal is often followed by rebound. Proteasome inhibitors (PIs) deplete antibody-p ...
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Journal ArticleAm J Transplant · August 2017
Early activation of coagulation is an important factor in the initiation of innate immunity, as characterized by thrombotic microangiopathy (TMA). In transplantation, systemic anticoagulation is difficult due to bleeding. A novel "cytotopic" agent, thromba ...
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Journal ArticleJ Am Soc Nephrol · July 2017
Featured Publication
The efficacy of bortezomib monotherapy in desensitizing kidney transplant candidates with preformed donor-specific antibodies remains unclear. We evaluated the effect of bortezomib on preformed antibodies and upstream components of the B cell response in a ...
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Journal ArticleTransplantation · April 2017
Crosstalk between B and T cells in transplantation is increasingly recognized as being important in the alloimmune response. T cell activation of B cells occurs by a 3-stage pathway, culminating with costimulation signals. We review the distinct T cell sub ...
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Journal ArticleBiomaterials · March 2017
Trauma patients produce a host of danger signals and high levels of damage-associated molecular patterns (DAMPs) after cellular injury and tissue damage. These DAMPs are directly and indirectly involved in the pathogenesis of various inflammatory and throm ...
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Journal ArticleJ Am Soc Nephrol · January 2017
An individual's immune function, susceptibility to infection, and response to immunosuppressive therapy are influenced in part by his/her T cell maturation state. Although childhood is the most dynamic period of immune maturation, scant information regardi ...
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Journal ArticleAm J Transplant · September 2016
Previously, we demonstrated that alemtuzumab induction with rapamycin as sole maintenance therapy is associated with an increased incidence of humoral rejection in human kidney transplant patients. To investigate the role of rapamycin in posttransplant hum ...
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Journal ArticleAm J Transplant · June 2016
We have established a model of sensitization in nonhuman primates and tested two immunosuppressive regimens. Animals underwent fully mismatched skin transplantation, and donor-specific antibody (DSA) response was monitored by flow cross-match. Sensitized a ...
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Journal ArticleTransplantation · December 2015
BACKGROUND: Blocking leukocyte function-associated antigen (LFA)-1 in organ transplant recipients prolongs allograft survival. However, the precise mechanisms underlying the therapeutic potential of LFA-1 blockade in preventing chronic rejection are not fu ...
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Journal ArticleAm J Transplant · March 2015
Featured Publication
Depletional strategies directed toward achieving tolerance induction in organ transplantation have been associated with an increased incidence and risk of antibody-mediated rejection (AMR) and graft injury. Our clinical data suggest correlation of increase ...
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Journal ArticleAm J Transplant · January 2014
De novo donor-specific antibody (DSA) after organ transplantation promotes antibody-mediated rejection (AMR) and causes late graft loss. Previously, we demonstrated that depletion using anti-CD3 immunotoxin combined with tacrolimus and alefacept (AMR regim ...
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Journal ArticleCold Spring Harb Perspect Med · July 1, 2013
Because lymphocytes were shown to mediate transplant rejection, their depletion has been studied as a mechanism of preventing rejection and perhaps inducing immunologic tolerance. Agents that profoundly deplete lymphocytes have included monoclonal antibodi ...
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Journal ArticleAm J Transplant · October 2012
Even though the etiology of chronic rejection (CR) is multifactorial, donor specific antibody (DSA) is considered to have a causal effect on CR development. Currently the antibody-mediated mechanisms during CR are poorly understood due to lack of proper an ...
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Journal ArticleAm J Transplant · September 2012
Chronic allograft rejection is a major impediment to long-term transplant success. Humoral immune responses to alloantigens are a growing clinical problem in transplantation, with mounting evidence associating alloantibodies with the development of chronic ...
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Journal ArticleSemin Immunol · April 2012
The role of antibodies in chronic injury to organ transplants has been suggested for many years, but recently emphasized by new data. We have observed that when immunosuppressive potency decreases either by intentional weaning of maintenance agents or due ...
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Journal ArticleJ Immunol · October 15, 2011
Grafts can be rejected even when matched for MHC because of differences in the minor histocompatibility Ags (mH-Ags). H4- and H60-derived epitopes are known as immunodominant mH-Ags in H2(b)-compatible BALB.B to C57BL/6 transplantation settings. Although m ...
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Journal ArticleTransplantation · April 27, 2010
BACKGROUND: Interleukin (IL)-15 is a chemotactic factor to T cells. It induces proliferation and promotes survival of activated T cells. IL-15 receptor blockade in mouse cardiac and islet allotransplant models has led to long-term engraftment and a regulat ...
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OtherJ Clin Invest · April 2010
Belying the spectacular success of solid organ transplantation and improvements in immunosuppressive therapy is the reality that long-term graft survival rates remain relatively unchanged, in large part due to chronic and insidious alloantibody-mediated gr ...
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Journal ArticleTransplantation · October 27, 2009
Despite the success of immunosuppressive drug therapy to reduce the incidence of acute rejection in organ transplantation, chronic rejection is still an impediment to long-term graft survival and tolerance. There is a growing body of evidence that B-cell p ...
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Journal ArticleAm J Transplant · August 2009
Alemtuzumab is a monoclonal antibody that depletes T and B cells and is used as induction therapy for renal transplant recipients. Without long-term calcineurin inhibitor (CNI) therapy, alemtuzumab-treated patients have a propensity to develop alloantibody ...
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Journal ArticleTransplantation · June 27, 2009
BACKGROUND: Injuries in kidney transplant is currently diagnosed by needle biopsy. A noninvasive test that sensitively detects these injuries would benefit the patients. METHODS: Urine samples were collected from healthy controls and kidney transplant reci ...
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Journal ArticleAm J Transplant · May 2009
Alemtuzumab induction with 60 days of tacrolimus treatment and continuous sirolimus treatment prevented acute rejection in nine of 10 consecutive renal allograft recipients. All patients are alive with a functioning kidney graft at 27-39 months of follow-u ...
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Journal ArticleSemin Liver Dis · February 2009
Spontaneous acceptance of liver allografts occurs in several species. However, tolerance is rare in human transplant patients even though rejection is relatively easily reversed. Histological features of acute rejection in liver transplantation are similar ...
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Journal ArticleAm J Transplant · August 2008
Previous studies showed that absence of chemokine receptor Cxcr3 or its blockade prolong mouse cardiac allograft survival. We evaluated the effect of the CXCR3 receptor antagonist MRL-957 on cardiac allograft survival, and also examined the impact of anti- ...
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Journal ArticleJ Immunol · December 15, 2007
Chemokine-chemokine receptor interactions and the subsequent recruitment of T lymphocytes to the graft are believed to be among the initial events in the development of acute and chronic rejection of heart transplants. We sought to determine the role of ch ...
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Journal ArticleJ Immunol · November 15, 2007
We hypothesize that developmental exposure to noninherited maternal Ags (NIMA) results in alloantigen-specific natural and adaptive T regulatory (T(R)) cells. We compared offspring exposed to maternal H-2(d) (NIMA(d)) with nonexposed controls. In vitro ass ...
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Journal ArticleTransplantation · February 27, 2006
BACKGROUND: A fundamental limitation of in vitro immunologic tests in the field of transplantation is that existing functional tests poorly correlate with in vivo immune responses such as rejection, tolerance, or absence of rejection due to immunosuppressi ...
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Journal ArticleIEICE Transactions on Communications · January 1, 2006
A cell search technique utilizing a known postfix for OFDM (orthogonal frequency division multiplexing) cellular systems is described. The known postfix is generated in the time domain by inserting pilots in the frequency domain and plays the role of the c ...
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Journal ArticleTransplantation · October 15, 2004
BACKGROUND: CXCR3 binding chemokines play a key role in recruitment of inflammatory cells into an organ transplant. This study addresses the question of whether urinary excretion of these chemokines correlates with acute rejection in a baboon kidney transp ...
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