| BackgroundRenal transplantation is the most ideal therapy in patients with chronic renal failure. the History of renal transplantation in a sense is locked in battle with rejection of history. Rejection after renal transplantation is mainly composed of antigen recognition, lymphocyte proliferation, differentiation, target cells damage so caused a series of immune reaction. With the use of new immunosuppressant, the incidence of acute rejection decreased obviously, But clinical acute rejection caused by the risk of chronic renal allograft nephropathy is higher and higher. The data show that although the incidence of acute rejection to fall,But in view of the rejection of the antibody treatment increased significantly, the proportion of the; prompt Hint of acute rejection after kidney transplantation is still a big problem in clinical; The first hospital affiliated to zhejiang university school of medicine center,1200cases of kidney disease occurrence of acute rejection in renal transplant recipients;Found that significantly influence the occurrence of acute rejection in kidney transplant recipients long-term prognosis, Prognosis is worse happens many times rejection, After6months) late (transplantation rejection reactions in earlier for the poorer prognosis, high incidence of chronic renal allograft loss. Acute rejection is whether it is totally reversed significantly affect the prognosis of renal transplant recipients, which have not completely reversed in patients with chronic renal allograft loss after higher..Acute rejection is the important factors that affect graft survival and incidence ranged from20%to50%;Acute rejection will not only increase the incidence of early renal allograft loss and other complications and related cost of treatment, and it is the leading cause of late graft loss is an important independent risk factors. To prevent and reduce the occurrence of early acute rejection for transplant recipients and the long-term graft survival. Alemtuzumab is the main target cells in a role of T lymphocytes.Alemtuzumab originally used in the treatment of chronic lymphocytic leukemia, then used in the treatment of multiple sclerosis, autoimmune diseases such as rheumatoid arthritis, vasculitis. In recent years, Alemtuzumab is applied to solid organ transplantation, America’s annual report shows:From2003to2003Alemtuzumab in solid organ transplantation, there is an upward trend in the application.In2006in various kinds of solid organ transplant recipients with Alemtuzumab proportion is:small intestine transplantation21.4%21.4%13.4%, pancreas transplantation, renal transplantation, lung transplantation, heart transplantation, liver transplantation,1.7%and1.4%7.2%. Calne, etc for the first time since1998, reported Alemtuzumab induction of immune tolerance after treatment for a kidney transplant, Alemtuzumab induction of immune tolerance treatment gradually caused widespread concern in the field of organ transplantation.Alemtuzumab is a kind of humanized mice CD52monoclonal IgG1antibody immune inhibitors. CD52small molecules on the cell membrane surface glycoprotein, is widely expressed on T lymphocytes and B lymphocytes, natural killer cells, mononuclear cells such as immune cell membrane surface. Alemtuzumab is quickly remove graft receptors on peripheral blood T lymphocytes and B lymphocytes, although make the receptor can identify the donor antigen immune response but can only occur, rather than rejection. Eventually, Alemtuzumab through selective removal of donor antigen immune response of T lymphocyte and B lymphocyte clones, the receptors of graft immune tolerance Recent studies have shown that Alemtuzumab there may be other important role in the induction of immune tolerance mechanism. Kidney transplant recipients with alemtuzumab after peripheral blood CD4+CD25+FOXP3+regulatory T cells in5and memory T cells proliferation. Regulatory T cell proliferation is advantageous to the induction and maintenance of transplantation tolerance and CD28-CD8+memory T cells proliferation competitive inhibition of CD4+T cells and delay the cells of CD4+T cell mediated immune recovery. The study also found that after kidney transplant recipients who use alemtuzumab peripheral blood dendritic cells decreased, myeloid dendritic cells7sample/plasma cells, dendritic cells proportion decreased. Dendritic cells as antigen presented the induction of T cell immune response after transplantation, myeloid dendritic cells mediated by T cells to Thl differentiation, plasma cells, T dendritic cells mediated by T cell to Th2differentiation. Therefore Alemtuzumab may be mediated by inhibition of dendritic cells to Thl differentiation of T cells and dendritic cells mediated by T cell to Th2differentiation pathway regulating acquired immune tolerance.In clinical renal transplantation application, Alemtuzumab often with cyclosporina, FK506, corticosteroids, azathioprine, or mycophenolate mofetil combined, in order to achieve satisfactory result of immunosuppression.ObjectiveTo study the effect of Alemtuzumab, a humanized CD52monoclonal antibody, on the prevention of acute rejection and promoting graft and patient survival in renal allograft recipients.MethodsThis experment follows a meta analysis of randomized controlled experiment related guide to collection and analysis data, collect the data of randomized controlled trials obout the effect of Alemtuzumab on renal graft rejection and survival,since January1998to May2012,the standard of the data include:1. randomized controlled trial;2.experiments in the same period of the control group;3.the same intervention measures.we use the Jadad literature research and the quality criteria to evaluation the quality of the data.Random effects meta-analysis and relative risk were used to estimate.Heterogeneity was assessed using the Cochran’s Q test and the Higgins I-squared statistic (I2),Sensitivity analyses were carried out to characterize possible sources of statistical heterogeneity, by excluding studies one-by-one.group analyses based on duration of follow-up, renal graft and patient survival,were conducted to identify the risk-subgroup interactions that could explain the inter-study differences. The statistical analyses were performed with RevMan5.1software. statistics data using M-H method, the risk ratio (RR).All the p values were two tailed, and p values<0.05were considered statistically significantResultsA total of9pertinent research articles were reviewed, including1paperswritten by Chinese authors and8by foreign authors. Meta-analysis of pooled results indicated that Alemtuzumab prevented the recipients of kidney transplantation from acute rejection effectively with half year prevention of RR0.42and95%CI0.29-0.62(P<0.01), and one year prevention of RR0.49,95%CI0.35-0.69(P<0.01), and two year prevention of RR0.73,95%CI0.53-1.02(P=0.06). It was revealed that Alemtuzumab could reduce the incidence of acute rejection by55%in half year,51%in one year and28%in two year. No statistical difference of graft and patient survival was found between Alemtuzumab and control group (RR=1.01,95%CI (0.98,1.05), P=0.47and RR=1.00,,95%CI(0.97,1.02), P=0.85), implying that Alemtuzumab did not throw an influence on graft and patient survival.ConclusionsAlemtuzumab may effectively prevent the recipients of kidney transplantation from acute rejection. No statistical difference of graft and patient survival exists between the patients receiving Alemtuzumab treatment and control group. |
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