Cardiac allograft rejection
ABSTRACT Success in cardiac transplantation has been achieved by the development of improved immunosuppressive therapies, which have led to a concomitant decrease in cardiac allograft rejection and infection. Rejection however continues to be the cause of significant morbidity and mortality particularly in the first year after cardiac transplantation. The endomyocardial biopsy remains an essential tool for its diagnosis. Acute cellular rejection has been a well recognized phenomenon although more recently, the diagnosis of antibody-mediated rejection has gained acceptance, a condition associated with greater graft dysfunction, subsequent development of cardiac allograft vasculopathy and mortality. In this article we review the current status of the diagnosis of cardiac allograft rejection as determined by the traditional endomyocardial biopsy, the more recent advances in the non-invasive evaluation of rejection, detection of circulating antibodies and the treatment of rejection.
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ABSTRACT: Cardiac allograft vasculopathy (CAV) is the leading cause of late morbidity and mortality in heart-transplant patients. Increasing evidences support the important role of chemokines and their receptors in transplant immunology. Chemokine-chemokine receptor interaction and subsequent recruitment of T-lymphocytes to the graft are early events in the development of chronic rejection of transplanted hearts. In this study, we first inhibited CC-motif chemokine receptor 5 (CCR5) expression by using lentiviral-mediated gene transfer of an anti-CCR5 siRNA, which introduced through CD34(+) hematopoietic stem/progenitor cell transplantation. Stably marked lymphocytes expressing siRNA and consistent downregulation of CCR5 expression were detected. Our results showed that survival was significantly prolonged in CCR5 knock-down mice and donor hearts from siRNA-treated mice developed markedly less CAV. Infiltration of CD4(+) and CD8(+) T-lymphocytes into transplanted hearts was also markedly decreased. These findings suggest that CCR5 plays an important role in CAV development and inhibition of this chemokine could improve long-term survival after cardiac transplantation.Transplant Immunology 11/2011; 26(2-3):128-32. DOI:10.1016/j.trim.2011.11.005 · 1.83 Impact Factor
Article: Inflammation in Myocardial Diseases[Show abstract] [Hide abstract]
ABSTRACT: Inflammatory processes underlie a broad spectrum of conditions that injure the heart muscle and cause both structural and functional deficits. In this article, we address current knowledge regarding 4 common forms of myocardial inflammation: myocardial ischemia and reperfusion, sepsis, viral myocarditis, and immune rejection. Each of these pathological states has its own unique features in pathogenesis and disease evolution, but all reflect inflammatory mechanisms that are partially shared. From the point of injury to the mobilization of innate and adaptive immune responses and inflammatory amplification, the cellular and soluble mediators and mechanisms examined in this review will be discussed with a view that both beneficial and adverse consequences arise in these human conditions.Circulation Research 01/2012; 110(1):126-44. DOI:10.1161/CIRCRESAHA.111.243170 · 11.09 Impact Factor
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ABSTRACT: Acute cellular rejection (ACR), antibody-mediated rejection (AMR), and cardiac allograft vasculopathy (CAV) are important limitations for the long-term survival of heart transplant recipients. Although much progress has been made in reducing ACR with modern immunosuppressive treatments and continuous biopsy surveillance, there is still a long way to go to better understand and treat AMR, to enable early detection of patients at risk of CAV, and to reduce the development and sustained progression of this irreversible disease that permanently compromises graft function. This review considers the advances made in ACR detection and treatment allowing a more prolonged survival and the risk factors leading to endothelial injury, dysfunction, inflammation, and subsequent CAV, as well as new treatment modalities for CAV. The review also evaluates the controversies around the definition, pathogenesis, and treatment of AMR. To date, much progress is still needed to significantly reduce post-transplant complications and increase graft and patient survival.04/2012; 159(4):238-51. DOI:10.1016/j.trsl.2012.01.018