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.
Long-term survival after lung transplantation (LTx) is hampered by chronic lung allograft dysfunction (CLAD). Our study aimed to evaluate prevalence and prognostic importance of obstructive and restrictive CLAD phenotypes with or without identifiable underlying cause to validate the recently proposed classification system for CLAD.
In this study, 22 patients were transplanted with preexisting DSA, and 43 patients developed ndDSA posttransplant. Pretransplant (P
Pediatric heart transplant waitlist mortality remains significant but allograft offer refusals are common and allografts continue to be discarded.
Lung transplantation (LTx) recipients have 1-, 5-, and 10-year unadjusted survival rates of 80%, 54%, and 32%, respectively.1 Chronic lung allograft dysfunction (CLAD) causes most deaths after the first post-transplant year,1 –3 and most CLAD has an obstructive phenotype known as bronchiolitis obliterans syndrome (BOS).4 Obliterative bronchiolitis (OB), the histologic hallmark of BOS, consists of a fibrotic luminal obliteration of the respiratory and terminal bronchioles.5 The patchy nature of OB reduces the diagnostic sensitivity of transbronchial lung biopsies.
Blood type O lung allografts may be allocated to either blood type identical (type O) or compatible (Non-O) candidates. We tested the hypothesis that the current organ allocation schema in the U.S. - based on the LAS - prejudices against the allocation of allografts to type O candidates, given that the pool of potential donors is smaller.
Adults with congenital heart disease (ACHD) represent a growing, albeit still small, proportion of heart transplant (HT) recipients (1, 2). These patients frequently present with complex anatomy and physiology, and atypical manifestations of cardiac failure. Despite being younger than other HT candidates, they have higher risk for adverse outcomes early after HT. This relates to prior thoracic operations, longer allograft ischemic time, a high prevalence of sensitization, less frequent use of pre-transplant mechanical circulatory support (1), and underappreciated end-organ dysfunction.
Cardiac allograft vasculopathy (CAV) remains a prevalent morbidity following heart transplantation1 According to the registry of the International Society of Heart and Lung Transplantation (ISHLT), CAV is detectable increasingly by the post-transplant year (e.g. 8% in the first year, 32% in the 5 years and 43% in the 8 years).2 Ensuing allograft failure from CAV eventually accounts for 30% of recipient deaths 5 years after transplantation. The pathogenesis of CAV involves immune- and non-immune-mediated mechanisms that lead to endothelial cell injury, followed by intimal hyperplasia, vascular remodeling and subsequent coro...
AbstractPurpose of ReviewThe first human lung transplant surgery in the world was done in 1963, followed by the first heart transplant in 1967, making this year its 50th anniversary. Since then, there has been great advancement in immunotherapy, with the adoption of calcineurin inhibitors (CNI), mycophenolate mofetil, and proliferation signal inhibitors (PSI). However, while these medications are crucial to maintenance of allograft function and prevention of allograft rejection, they have many toxicities and side effects, which make therapeutic dose monitoring and recognition of drug-drug interactions of critical importanc...
This thirty-fifth adult lung and heart –lung transplant report summarizes data from 64,803 adult lung and 4,054 adult heart-lung transplants performed through June 30, 2017 and reported to the International Thoracic Organ Transplant Registry. With each year's report we now also provide more detailed analyses on a particular focus theme . Since 2013, these have been donor and recipient age; retransplantation; early graft failure; indication for transplant; and allograft ischemic time; and in 2018, multiorgan transplantation.
In a recently published article, Asleh et al. demonstrated that cardiac allograft recipients with a baseline serum urate higher than 7 mg/dL are at a two-fold higher risk for developing cardiac allograft vasculopathy (CAV) and that the increase in serum urate during follow-up is associated with plaque progression independently of renal function, sirolimus therapy, and other comorbidities. Εven though there are data about the role of urate in endothelial dysfunction and inflammation, the authors conclude that although serum urate may be a reliable biomarker for CAV progression, its implication in the pathogenesis of...