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: Suppressor of cytokine signaling 3 (SOCS3) is the main negative feedback regulator of cytokine signals. We investigated the hypothesis that overexpression of SOCS3 in a murine cardiac allograft transplantation model may result in a survival advantage of the allograft by attenuating alloreactive T-cell responses. With the use of BALB/c (H-2(d) ) donor mice and C57Bl/6j (H-2(b) ) recipient mice, the murine cardiac transplantation model was established. Recipient mice received tail intravenous injection with eukaryotic expression plasmid pEF-FLAG-I/mSOCS3 before and after transplantation. Heart beat of the grafts and immune responses were monitored. Overexpression of SOCS3 within grafts and spleens can prolong the survival time of cardiac allograft through attenuating inflammatory cells infiltration such as T cells and macrophages in the grafts, decreasing the number of CD4(+) IL-17(+) cells and CD8(+) IL-17(+) cells in spleens, and reducing the expression of STAT3 in grafts and phosphorylation of STAT3 in both grafts and spleens. Overexpression of SOCS3 significantly delays cardiac allograft acute rejection, which is associated with reduced allograft proinflammatory leukocytes infiltration and impaired alloreactive IL-17(+) T cell immunity. This article is protected by copyright. All rights reserved.The Journal of Gene Medicine 03/2014; · 2.16 Impact Factor
Article: Antibody-mediated rejection.[Show abstract] [Hide abstract]
ABSTRACT: The diagnosis of antibody-mediated rejection (AMR) has been revolutionized in recent years by advances in the detection of human leukocyte antigen (HLA) and non-HLA antibodies and by the standardized classification of histologic and immunologic changes in endomyocardial biopsies. The treatment of AMR is also undergoing significant development with targeted use of therapies directed at antibody production and function. The diagnosis of AMR achieved greater standardization after a consensus conference in 2010. By the proposed classification, endomyocardial biopsies are now graded on the basis of the severity of histologic and immunologic changes. Management of AMR is often complicated, as patients may have persistent symptoms after treatment, including a reduction in ejection fraction, restrictive physiology leading to recurrent heart failure, and accelerated progression of transplant coronary artery disease. We often rely on therapies to reduce the levels of donor-specific anti-HLA antibodies, including rituximab and bortezomib, as well as photopheresis to alter the function of T cells, although such patients may go on to require redo transplantation. AMR offers challenges of diagnosis and management, but recent advances in the detection of antibodies, the interpretation of endomyocardial biopsies, and the use of therapies directed toward antibody production offer great promise. In the future, standardization of management across transplant centers will allow for clinical trials of the effectiveness of these therapies.Current opinion in organ transplantation 08/2012; 17(5):551-7. · 3.27 Impact Factor
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ABSTRACT: Immunosuppressive drugs used in the management of heart and lung transplants have a large monetary and quality of life cost due to their side effects. Total lymphoid irradiation (TLI) is one method of minimising the need for or replacing post-operative immunosuppressive drugs. A literature review was conducted on electronic databases using defined search terms. The aim was to establish the indications for the use of TLI, its advantages and disadvantages and the weaknesses associated with the methods used in related research. Eight articles were located that focused on TLI usage in combating organ rejection. These studies identified that the use of TLI resulted in a reduction in early rejection. One study reported a drop in rejection episodes from 0.46 to 0.14 episodes per patient per month once the TLI was complete. While the short-term prognosis is excellent, the long-term outlook is less positive with an increased risk of organ rejection and myelodysplasia 3.5 years post-TLI. This review reminds us that radiation therapy (RT) is not exclusively indicated for cancer treatment. While TLI cannot replace immunosuppressive drug therapy, it can offer a treatment option for people that cannot tolerate immunosuppressive drugs, or when conventional anti-rejection treatment is no longer viable. Reported long-term complications suggest that TLI should be used with caution. However, this modality should not be overlooked in cases of chronic rejection. Further research is required to establish the efficacy of RT in the treatment of transplant patients who are unsuitable for drug-based anti-rejection therapies.Journal of Medical Radiation Sciences. 07/2014;