Thoracic Organ Transplantation: Laboratory Methods
Although great progress has been achieved in thoracic organ transplantation through the development of effective immunosuppression, there is still significant risk of rejection during the early post-transplant period, creating a need for routine monitoring for both acute antibody and cellular mediated rejection. The currently available multiplexed, microbead assays utilizing solubilized HLA antigens afford the capability of sensitive detection and identification of HLA and non-HLA specific antibodies. These assays are being used to assess the relative strength of donor specific antibodies; to permit performance of virtual crossmatches which can reduce the waiting time to transplantation; to monitor antibody levels during desensitization; and for heart transplants to monitor antibodies post-transplant. For cell mediated immune responses, the recent development of gene expression profiling has allowed noninvasive monitoring of heart transplant recipients yielding predictive values for acute cellular rejection. T cell immune monitoring in heart and lung transplant recipients has allowed individual tailoring of immunosuppression, particularly to minimize risk of infection. While the current antibody and cellular laboratory techniques have enhanced the ability to manage thoracic organ transplant recipients, future developments from improved understanding of microchimerism and graft tolerance may allow more refined allograft monitoring techniques.
This article summarizes recent knowledge and clinical advances in machine perfusion (MP) of thoracic organs. MP of thoracic organs has gained much attention during the last decade. Clinical studies are investigating the role of MP to preserve, resuscitate, and assess heart and lungs prior to transplantation. Currently, MP of the cardiac allograft is essential in all type DCD heart transplantation while MP of the pulmonary allograft is mandatory in uncontrolled DCD lung transplantation. MP of thoracic organs also offers an exciting platform to further investigate downregulation of the innate and adaptive immunity prior to r...
Cardiac allograft vasculopathy (CAV) is a major complication after heart transplantation (HT). Uric acid (UA) may play a role in CAV due to its role in stimulating T cell-mediated immunity. Sirolimus is associated with CAV attenuation through a number of mechanisms including immune-mediated effects. We aimed to determine whether UA is an independent predictor of CAV and whether conversion to sirolimus as primary immunosuppression modulates UA levels.
Cardiac allograft vasculopathy (CAV) is a leading cause of re-transplantation and death in pediatric heart transplant recipients.1 CAV is a complex process involving alloimmune response, chronic inflammation, and smooth muscle cell proliferation, exemplifying cross talk between cytokines and growth factors.2 The diagnosis of CAV is challenging: early in the development of CAV, patients are almost universally asymptomatic. Thus, despite the invasive nature, coronary angiography is performed on a routine schedule for CAV surveillance.
Optical coherence tomography (OCT) –based studies of cardiac allograft vasculopathy (CAV) published thus far have focused mainly on frame-based qualitative analysis of the vascular wall. Full capabilities of this inherently 3-dimensional (3D) imaging modality to quantify CAV have not been fully exploited.
Optical coherence tomography (OCT) based studies of cardiac allograft vasculopathy (CAV) published thus far have mainly focused on frame-based qualitative analysis of the vascular wall. Full capabilities of this inherently 3D imaging modality to quantify CAV have not been fully exploited.
BACKGROUND: HLA-DQ donor-specific antibodies (DSA) are implicated in allograft dysfunction after renal and lung transplantation. Limited data exists on the impact of HLA-DQ antibodies on heart transplant patients. OBJECTIVE: To investigate the impact of DSA formation on allograft function and outcomes in heart transplant patients. DESIGN:Retrospective cohort study. SETTING:Collating post-transplantation patient data from computerized database in a tertiary hospital in Riyadh, Saudi Arabia from January 2006 to October 2014. PATIENTS AND METHODS:We excluded recipients with positive preoperative comp...
Heart transplantation (HTx) remains the ultimate treatment for selected end-stage heart failure patients. Over time, patient selection and pre- and post-operative management have improved along with immunosuppressive therapy. However, these efforts have failed to improve outcome following the first post-transplant year. Analysis of International Society for Heart and Lung Transplantation registry data shows that cardiac allograft vasculopathy (CAV) and graft failure are the major heart-related late mortality causes following HTx .
We have achieved tolerance of cardiac allografts in cynomolgus monkeys for the first time by using a mixed chimerism-based conditioning protocol and by co-transplanting a donor kidney. The mechanism by which a kidney confers tolerance upon a heart is unclear. To gain mechanistic insight and at the same time develop a clinically relevant tolerance protocol, we investigated whether a vascularized donor thymus could substitute for the donor kidney.
Cytomegalovirus (CMV) infection after heart transplantation is considered as risk factor for the development of cardiac allograft vasculopathy (CAV), a serious long-term complication after heart transplantation. In previous work we could show that murine CMV infection (MCMV) leads to increased levels of CAV. MCMV genome encodes the G protein-coupled receptor (GPCR) M33 which is associated with virus latency and replication in the host. Therefore we analyzed if M33 knockout could prevent CMV induced CAV development.
The SCHEDULE trial investigated whether initiation of the proliferation signal inhibitor everolimus and early cyclosporine avoidance could improve renal function and reduce cardiac allograft vasculopathy in de-novo heart transplant recipients. After 12 months, we reported significantly higher measured glomerular filtration rates (mGFR) among patients treated with everolimus vs. conventional cyclosporine (79.8 ±17.7 vs. 61.5±19.6 mL/kg/1.73 m2; p