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Cardiac Allograft Recipients (cardiac + allograft_recipient)
Selected AbstractsIncreased Expression of p53 Protein Correlates With the Extent of Myocyte Damage in Cardiac Allograft RejectionCONGESTIVE HEART FAILURE, Issue 6 2008Bernadette K. McLaren MD Acute cardiac allograft rejection (ACAR) has been associated with a poor prognosis. The early diagnosis of ACAR necessitates the accurate detection of myocyte damage. Nuclear damage activates p53, a transcription factor that initiates apoptosis and repair. Endomyocardial biopsies (n=25) from 10 cardiac allograft recipients were stained for nuclear p53. The biopsies were divided into rejection groups based on the grading of ACAR: group 1, grade 0; group 2, grade Ia and Ib; group 3, grades II and III. While clinical indices did not correlate with myocyte damage, significantly more myocytes in group 3 stained for nuclear p53 (2.48±0.60/mm2) compared with group 1 (0.22±0.12/mm2) and group 2 (0.43±0.18/mm2). Increased expression of p53 in cardiac myocytes with grade II or grade III rejection provides an objective quantification as an aid in the diagnosis of ACAR. [source] Dissection of the CMV specific T-cell response is required for optimized cardiac transplant monitoring,JOURNAL OF MEDICAL VIROLOGY, Issue 9 2008Alexander Kirchner Abstract Despite the success of antivirals in preventing clinically overt CMV disease in cardiac allograft recipients, sub-clinical active CMV infection remains a major concern because of its association with allograft rejection and vasculopathy. The measurement of CMV specific T-cell responses is a promising approach to assessing this situation. For simplicity, class-I MHC/peptide-multimers staining CD8 T-cells directly are often used but this ignores a much wider range of responses including the whole CD4 T-cell compartment. CD4 T-cells, however, were recently shown to be critical to reducing CMV load early after transplantation. To determine how extensive T-cell responses to CMV are, the responses to two dominant CMV proteins, IE-1 and pp65, were dissected in detail accounting for T-cell lineage, frequencies, epitope recognition and changes over time in more than 25 heart transplant recipients. Cross-sectional results from over 30 healthy CMV-carriers were analyzed for comparison. Responses were unexpectedly complex, with considerable inter-individual variation in terms of dominance, breadth, and recognized epitopes. Whereas the use of MHC/peptide-multimers for clinical CD8 T-cell response monitoring alone can be justified in some situations, short term T-cell activation combined with intracellular cytokine staining was clearly found to be of more general usefulness. The performance of IFN-gamma, TNF-alpha, or IL-2 as single read-outs in identifying activated T-cells was examined and confirmed that the frequently used IFN-gamma was best suited. These results should be used to inform the design of clinically applicable and diagnostically useful approaches to monitoring CMV specific responses in heart transplant recipients. J. Med. Virol. 80:1604,1614, 2008. © 2008 Wiley-Liss, Inc. [source] Breaking Down Donor-Reactive T-Cell Activation to Two StepsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009E. D. Poggio In mouse cardiac allograft recipients, donor-reactive CD8 T cells proliferate without development to efffector function in the absence of CD154 costimulation. See article by Shah et al on page 2697. [source] Critical Role for IL-6 in Hypertrophy and Fibrosis in Chronic Cardiac Allograft RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009J. A. Diaz Chronic cardiac allograft rejection is the major barrier to long term graft survival. There is currently no effective treatment for chronic rejection except re-transplantation. Though neointimal development, fibrosis, and progressive deterioration of graft function are hallmarks of chronic rejection, the immunologic mechanisms driving this process are poorly understood. These experiments tested a functional role for IL-6 in chronic rejection by utilizing serial echocardiography to assess the progression of chronic rejection in vascularized mouse cardiac allografts. Cardiac allografts in mice transiently depleted of CD4+ cells that develop chronic rejection were compared with those receiving anti-CD40L therapy that do not develop chronic rejection. Echocardiography revealed the development of hypertrophy in grafts undergoing chronic rejection. Histologic analysis confirmed hypertrophy that coincided with graft fibrosis and elevated intragraft expression of IL-6. To elucidate the role of IL-6 in chronic rejection, cardiac allograft recipients depleted of CD4+ cells were treated with neutralizing anti-IL-6 mAb. IL-6 neutralization ameliorated cardiomyocyte hypertrophy, graft fibrosis, and prevented deterioration of graft contractility associated with chronic rejection. These observations reveal a new paradigm in which IL-6 drives development of pathologic hypertrophy and fibrosis in chronic cardiac allograft rejection and suggest that IL-6 could be a therapeutic target to prevent this disease. [source] Lack of Effect of MICA Antibodies on Graft Survival Following Heart TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009J. D. Smith Little is known about the effect of MICA antibodies (Abs) on cardiac allograft function and survival. Pretransplant and posttransplant serum from 491 and 196 adult cardiac allograft recipients, respectively, has been investigated for MICA Abs, donor specificity and the effect of MICA Abs on graft survival, acute rejection episodes (AR) and cardiac allograft vasculopathy (CAV). Patients with HLA Abs (11.6%) were excluded from the analysis. A total of 11.8% of patients had MICA Abs, without HLA Abs, before their transplant. Actuarial graft survival demonstrated slightly better survival of patients with donor-specific MICA Abs at 1 and 5 years (88.9% and 83.3%) than patients negative for MICA Abs (72% and 63.7%, p = 0.051). After transplantation, 15.8% of patients produced MICA Abs, and in 17 patients these were produced de novo. There was no effect of pretransplant or posttransplant production of MICA Abs on numbers of AR episodes in year 1, or CAV assessed at years 3 and 5. Immunocytochemistry of cardiac biopsies from 11 patients did not demonstrate a presence of MICA. Sera from only 4/69 patients with MICA Abs fixed complement prior to transplantation and from 7/38 patients following transplantation. In conclusion, this study suggests that MICA Abs do not adversely affect the outcome of cardiac transplantation. [source] Immunohistochemical Model to Predict Risk for Coronary Artery Disease and Failure in Heart Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2001Carlos A. Labarrere Transplant coronary artery disease is the leading cause of long-term morbidity and mortality in cardiac transplantation. We developed a model for early identification of patients who subsequently develop coronary artery disease and graft failure. Serial biopsies obtained from 141 cardiac allografts (5.5 ± 0.1 biopsies/patient) during the first 3 months post-transplant were evaluated immunohistochemically for deposition of myocardial fibrin, depletion of arteriolar tissue plasminogen activator, presence of arterial/arteriolar endothelial activation markers, and changes in vascular antithrombin. An immunohistochemical risk score was developed with a minimum value of 0 (normal) and a maximum value of 4 (most abnormal). Scores of 0 (low risk), 0.5,3.0 (moderate risk), and 3.5,4.0 (high risk) were analyzed for association with graft failure and development, severity, and progression of coronary artery disease detected using serial coronary angiograms (3.9 ± 0.2/patient). Allografts with high immunohistochemical risk scores in the first 3 months post-transplant developed more coronary artery disease (p,<,0.001), developed coronary artery disease earlier (p,<,0.001), developed more severe disease (p,<,0.001), and showed more disease progression (p,<,0.001) than allografts with moderate or low scores. Allografts with high immunohistochemical risk scores in the first 3 months post-transplant failed more (p,<,0.001) and failed earlier (p,<,0.001) than allografts with moderate or low scores. The present study demonstrates that early changes in the microvasculature are associated with impending coronary artery disease and graft failure in cardiac allograft recipients and suggests that treatment needs to be instituted early after transplantation in order to improve outcome. [source] | ||||||||||