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.
Source: Springer protocols feed by Immunology - Category: Allergy & Immunology Source Type: news

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We have applied cutting-edge mass cytometry (MC) technology to serial bronchoalveolar lavage (BAL) cells obtained from lung transplant recipients (LTRs) and have used it to compare the cellular composition of the BAL compartment in patients who remain stable or go on to develop lung allograft dysfunction (LAD), defined here as a drop, from any cause, in the forced expiratory volume in 1 second of 20% from the best post-transplant baseline value.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: 17 Source Type: research
We examined the ratio of regulatory T cells (Tregs, which express Foxp3) to T effector cells (Teff) in TBBx as a predictor of outcome.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: 16 Source Type: research
Long-term survival after lung transplantation (LTx) is hampered by chronic lung allograft dysfunction, with bronchiolitis obliterans syndrome (BOS) as its most common phenotype. Bronchiectasis (BRECT), hyperinflation and airtrapping are considered the key features of BOS on chest CT. We investigated whether chest CT and key features have prognostic value at BOS diagnosis in patients with established BOS after LTx.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: 15 Source Type: research
Chronic Allograft Dysfunction (CLAD) with Bronchiolitis obliterans (BOS) phenotype is a major limitation for long term survival after lung transplantation (LT). Predictive biomarkers for BOS are unavailable. Purpose of our study was to establish a tractable system to evaluate the effects of pre-transplant antibodies to self-antigens (AutoAbs) and to examine specific patterns that correlate with BOS.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: 14 Source Type: research
Chronic lung allograft dysfunction (CLAD) is a clinical/functional diagnosis that cannot be defined by histology in transbronchial biopsies (TBBs). Moreover, understanding the biology of CLAD is crucial for prevention and potential treatment. We studied gene expression associated with CLAD in TBBs, but also studied mucosal biopsies from the third bronchial bifurcation (3BMBs).
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: 13 Source Type: research
The DLCO measures the capacity of the lungs to exchange gas across the alveolar-capillary interface. We hypothesized that DLCO is a sensitive measure of injurious allograft processes that can disrupt this interface. Our goals were to describe the trajectory of DLCO measurements after lung transplantation, and to determine the prognostic significance of DLCO on chronic lung allograft dysfunction (CLAD) and survival.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: 12 Source Type: research
Chronic Lung Allograft Dysfunction (CLAD) is characterized by airway epithelial damage and fibrosis. The origin and initiation of fibrosis are poorly understood. We hypothesized that immune mediators in bronchoalveolar lavage (BAL) predict bronchiolitis obliterans syndrome (BOS), a form of CLAD, and poor survival. In a multi-center observational study, we investigated the role of proinflammatory cytokines as biomarkers for poor outcome after lung transplant (LTx).
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: 126 Source Type: research
Cardiac allograft vasculopathy (CAV) is a prevalent cause of graft failure and has remained so despite advances in HLA matching and immunosuppression in recent decades. Several distinct pathologic phenotypes of CAV have been described (Lu et al JHLT 2011 and Huibers et al Atherosclerosis 2014), but the correlation of these phenotypes to clinical features has been limited. Of particular interest in this study are patients who develop accelerated CAV, since this presentation is so clinically devastating but also because it may provide important mechanistic insights into CAV initiation and progression.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: 120 Source Type: research
Antibody mediated rejection (AMR) continues to be a major complication after heart transplantation (OHT) and poses a risk for allograft failure, graft vasculopathy and mortality. Diagnostic criteria for AMR have evolved over the years. Incidence of AMR is estimated to be 11-20% after OHT. We sought to evaluate the histological characteristics of AMR in endomyocardial biopsies (EMB) of deceased pediatric patients with positive HLA-associated antibodies.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: 119 Source Type: research
The goal of this study was to investigate the pathology of graft failure in a series of explants and autopsies with special emphasis on chronic lung allograft dysfunction (CLAD).
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: 118 Source Type: research
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