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Interleukin-2-producing helper T lymphocyte precursor frequency and rejection: a longitudinal cellular study after cardiac transplantation.

Interleukin-2-producing helper T lymphocyte precursors (HTLp) in the recipient recognize donor alloantigen expressed by the transplanted organ. The frequency of these reactive cells in the peripheral blood was determined and correlated with rejection episodes. Endomyocardial biopsy is generally used to quantify cardiac allograft rejection and guide immunotherapy. While non-invasive techniques have been investigated, none of these has demonstrated sufficient sensitivity or specificity to replace myocardial biopsy. Twelve cardiac transplant recipients were assessed over a 1 year period using lim…

Dithiothreitol treatment rescues C1q assay performance by reducing high background.

The presence of donor-specific antibodies (DSAs) to human leukocyte antigen (HLA) is associated with antibody-mediated rejection and reduced graft survival. Donor-specific HLA antibodies can bind to cells of the allograft and cause graft injury by activating the classical complement pathway. Antibodies capable of binding C1q, the first component of the classical complement pathway, are believed to be more detrimental to the graft. The C1q antibody assay is used to stratify the risk of antibody-mediated rejection. However, many patient samples exhibit extremely high background, rendering the te

Autologous and Allogenous Antibodies in Lung and Islet Cell Transplantation.

The field of organ transplantation has undoubtedly made great strides in recent years. Despite the advances in donor-recipient histocompatibility testing, improvement in transplantation procedures, and development of aggressive immunosuppressive regimens, graft-directed immune responses still pose a major problem to the long-term success of organ transplantation. Elicitation of immune responses detected as antibodies to mismatched donor antigens (alloantibodies) and tissue-restricted self-antigens (autoantibodies) are two major risk factors for the development of graft rejection that ultimatel…

Macrophage Actin Cytoskeleton in Chronic Rejection.

There is no cure for chronic rejection of transplanted organs. Macrophages are heavily involved in chronic rejection. Macrophages' movement into the graft depends on the actin cytoskeleton and its regulators the GTPase RhoA and its effector ROCK kinase. In this chapter, we describe how the interference with macrophage RhoA/ROCK pathway disrupts macrophage actin cytoskeleton, impairing their functions and migration to the allograft, and preventing the development of chronic rejection, and how such interference can be applied to clinical therapies.

31P nuclear magnetic resonance study of acute renal dysfunction in rat kidney transplants.

31P NMR spectroscopy was used to study renal allografts in rats subjected to allograft rejection, cyclosporine toxicity, ischemia, and ureteral obstruction. Parameters of relative peak areas and intracellular pH were accurately distinguished among the different causes of graft dysfunction. Ureteral obstruction was clearly identified by elevations in the phosphodiester/urine phosphate peak. Ischemia and rejection were both associated with increases in inorganic phosphates and phosphomonesters and decreases in the beta-phosphate peak of adenosine triphosphate but were distinguishable from each o…

Role of HLA compatibility in pediatric living-related liver transplantation.

BACKGROUND: Human leukocyte antigen (HLA) matching is, at present, not used for the allocation of cadaveric hepatic allografts because the liver is generally believed to be less susceptible to HLA-mediated rejection. However, the exact role of HLA compatibility in the long-term outcome of liver transplantation is not yet clearly defined. One of the advantages of living-related liver transplantation (LRLT) could be a better histocompatibility between donor and recipient. This study aimed at an assessment of the influence of HLA compatibility in a large series of LRLTs. METHODS: A total of 321

Immunosuppressive enzyme-responsive nanoparticles for enhanced accumulation in liver allograft to overcome acute rejection.

Acute rejection is a life-threatening complication after liver transplantation. Immunosuppressants such as tacrolimus are used to inhibit ac … ffolds. Intravenous administration of MMP9-responsive nanoparticles into a rat model of acute liver graft rejection results in enhanced nanoparticle accumulation in allograft as compared to nonresponsive nanoparticles. Consequently, the MMP9-responsive nanoparticles significantly inhibit intragraft inflammatory cell infiltration and proliferation, maintain intrag …

Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration.

The advent of more potent immunosuppressants led to the first successful human upper extremity transplantation in 1998. At this time, >100 upper extremity transplants, 30 face transplants, and a variety of other vascularized composite allotransplantation (VCA) procedures have been performed around the world. VCA recipients present unique challenges for transplantation. The incidence of acute rejection exceeds 80% in hand and face transplantation and is well documented, whereas reports about antibody-mediated rejection and chronic rejection remain scarce. Immunosuppression protocols commonly us

Conventional and Contrast-enhanced Ultrasound Imaging in 2 Human Kidney Xenotransplant Recipients.

BACKGROUND: Kidney xenotransplantation offers a promising novel solution to the global organ shortage, although the expected postoperative imaging characteristics remain undefined. METHODS: We report the first application of longitudinal grayscale, color, and spectral Doppler ultrasound in 2 human recipients of genetically engineered porcine kidney xenografts. One recipient additionally underwent serial contrast-enhanced ultrasound to assess parenchymal perfusion. Imaging findings were correlated with serum creatinine trajectories and biopsy-proven rejection. RESULTS: In both recipients, spe

Small intestine transplant immunologic risk assessment: More data is needed.

BACKGROUND: Intestinal transplantation (IT) remains the only treatment modality for patients with irreversible intestinal failure who cannot be maintained on chronic parenteral nutrition. Multiple reports have demonstrated an association between donor-specific antibodies (DSA) in IT graft rejection, however these studies have largely been single-center analyses. The goal of this study was to examine the available immunological data from the International Intestinal Transplant Registry (IITR) and evaluate the association with rejection. MATERIALS AND METHODS: Demographic, outcomes, and serolog…

The role of HLA-DRB1 matching in corneal grafting.

The aim of the study was to evaluate the role of HLA-DRB1 (Human Leukocyte Antigens) matching in corneal transplantation. Fifty-two patients … 2), keratoglobus (1), keratouveitis (1), corneal maculae (1), and corneal melting syndrome (1). The graft rejection frequency was higher in the group of high-risk patients (29%) than in the group of low risk patients (7.1%). The rejection rate of compatible grafts was 37% for high risk and 2% for low risk group, while the rejection rate of incompatible was 44% in …

Donor-derived cell free DNA as a biomarker in kidney transplantation.

The early detection of acute rejection in the allograft is important as it provides an opportunity for timely therapeutic intervention in order to preserve graft function and achieve longer graft survival. Donor-derived cell-free DNA (dd-cfDNA) has emerged as a new biomarker in the field of kidney transplantation. In this review, we used data from various studies to examine the role of dd-cfDNA in comparison to creatinine and donor-specific antibodies in the early detection of transplant rejection. We also reviewed the use of dd-cfDNA in other organ transplants as well as the challenges and po

Recent advances in renal transplantation: antibody-mediated rejection takes center stage.

Overlooked for decades, antibodies have taken center stage in renal transplantation and are now widely recognized as the first cause of allograft failure. Diagnosis of antibody-mediated rejection has considerably improved with identification of antibody-mediated lesions in graft biopsies and advances made in the detection of circulating donor-specific antibodies. Unfortunately, this progress has not yet translated into better outcomes for patients. Indeed, in the absence of a drug able to suppress antibody generation by plasma cells, available therapies can only slow down graft destruction. Th

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… The adaptive immune system comprises two distinct effector mechanisms—cytotoxic T cells and antibodies—and the question of which of these mechanisms contribute to graft rejection has been central from the very beginning of transplant immunology. …

Toll-like receptor 3 is an endogenous sensor of cell death and a potential target for induction of long-term cardiac transplant survival.

Inflammation posttransplant is directly linked to cell death programs including apoptosis and necrosis. Cell death leads to the release of cellular contents which can promote inflammation. Targeting of these pathways should be an effective strategy to prevent transplant rejection. Toll-like receptor 3 (TLR3) is emerging as a major endogenous sensor of inflammation. In this study, we assessed the role of TLR3 on cell death and transplant rejection. We showed that TLR3 is highly expressed on mouse microvascular endothelial cell (ECs) and the endothelium of cardiac grafts. We demonstrated that TL

Allogeneic bone marrow transplantation for severe aplastic anaemia--the London experience.

Using the Seattle protocol with minor modifications, 23 patients with severe aplastic anaemia received allogeneic bone marrow transplants fr … e overall results compare favourably with those from other transplant centres, but the high rate of graft rejection and low incidence of GVHD differ from other series. The results should encourage further referral of patients with severe AA for bone marrow transplantation.

Primary Epstein-Barr virus infection associated with a rejection episode in a human renal allograft recipient.

Five weeks after receiving a kidney donated by his brother, a 33 year old man showed signs of graft rejection concurrent with an Epstein-Barr virus infection. Primary infection with this virus has not been previousy documented in a renal transplant recipient and the possibility of a relationship between the infection and the kidney rejection is discussed.

The immunoreactive patient: Rejection and autoimmune disease.

1. Despite highly potent immunosuppression regimens, there is a small cohort of patients at risk of graft failure due to rejection. 2. Steroid-resistant rejection is managed by the escalation of immunosuppression, but only one-third of patients with chronic rejection respond to this approach. 3. Interferon therapy for recurrent hepatitis C may induce an immunoreactive state and increase rejection rates. 4. Cyclosporine reduces the risk of recurrence of primary biliary cirrhosis but does not alter survival rates. 5. Patterns of primary sclerosing cholangitis recurrence are not affected by immun

Lamellar keratoplasty using acellular porcine corneal stroma for the treatment of corneal ulcers.

OBJECTIVE: The study aimed to investigate the efficacy and safety of acellular porcine corneal stroma (APCS) for lamellar keratoplasty in the treatment of corneal ulcers. METHODS: A total of 14 patients (14 eyes) diagnosed with corneal ulcers who underwent lamellar keratoplasty using acellular porcine corneal stroma at the Second Affiliated Hospital of Nanchang University between June 2016 and May 2017 were recruited and followed up for at least 12 months. Postoperative visual acuity, epithelial recovery, graft transparency, the recurrence rate of corneal ulcers, the rate of graft rejection, …

De novo noncutaneous malignancies after kidney transplantation are associated with an increased risk of graft failure: results from a time-dependent analysis on 672 patients.

The aim of this study was to evaluate the association between cancer occurrence and risk of graft failure in kidney transplant recipients. From November 1998 to November 2013, 672 adult patients received their first kidney transplant from a deceased donor and had a minimum follow-up of 6 months. During a median follow-up of 4.7 years (3523 patient-years), 47 patients developed a nonmelanoma skin cancer (NMSC) and 40 a noncutaneous malignancy (NCM). A total of 59 graft failures were observed. The failure rate was 6 per 100 patient-year (pt-yr) after NCM versus 1.5 per 100 pt-yr in patients with

The prognostic utility of deceased donor implantation biopsy in determining function and graft survival after kidney transplantation.

BACKGROUND: Uncertainty remains in the prognostic utility of biopsies of deceased donor kidneys in predicting graft outcomes. METHODS: We examined implantation biopsies for 730 kidney transplant recipients from 491 deceased donors from 1990 to 2004. The median follow-up time was 5.1 years. Of the 730 transplants, 633 (86.7%) had implantation biopsies (wedge 89.1%). Of these 633, 541 (85.5%) could be assessed for % glomerulosclerosis (GS), interstitial fibrosis, tubular atrophy, arteriolar hyalinosis, and fibrous intimal thickening. Independent risk factors for delayed graft function include r