| Currently, the optimal treatment of end-stage renal disease (ESRD) is renal transplantation. Allograft rejection is still an important obstacle. Among kidney transplant rejection including hyperacule rejection, accelerated rejection, acute rejection and chronic rejection, acute rejection is the major complication following renal transplantation. Acute rejection remains a significant problem in clinical transplantation. In contrast, acute rejection is an important risk factor contributing to chronic rejection or chronic allograft dysfunction or chronic allograft nephropathy or late graft loss. Acute rejection or chronic rejection is a key problem which affect long-term allograft survival.Hyperacute rejection and accelerated rejection are associated with high panel reactive antibody (PRA >or = 50%) in highly sensitized patients awaiting transplantation who are sensitized to HLA antigens. These patients often have poor outcome after transplantation because of higher morbidity of hyperacute rejection, accelerated rejection, acute rejection or chronic rejection. To deal with sensitization is a worldwide problem. To explore molecular mechanisms of highly sensitization is necessary.Besides rejection, complication due to long treatment with immunosuppressive agents is serious. How to make good use of immunosuppressive agents needs insight of their molecular mechanisms and target genes.The rejection of an allograft is a complex and incompletely understood process. To understand rejection, it is necessary and important to understand the allogeneic immune response. Activation of alloreactive T cells and antigen-presenting cell (APC) is crucial. With the development of immunobiology, it is known that various genes involves activation of lymphocytes. There are more than 70 genes including oncogene, cytokine / cytokine receptor and other membran surface molecular gene. According to the time needed to express, these genes are divided into 3 groups: immediately genes (expressed within 15-30 minutes after stimulation), early genes (expressed within 0.5-24 hours) and late genes (expressed within several days). Many genes that code for signal transduction,inflammatory, adhesion, or effector molecules involve allogeneic immune response. There are many genes and signal transduction pathway in regulation of T cell activation.How to analysis hundreds or more genes in transplant immunity needs a powerful method such as recently developed DNA microarray technology. High-density microarray technology is a novel method for screening the expression of thousands of genes in a small tissue sample. This technique is well suited for studying allogeneic immune response and acute allograft rejection because alloimmune responses are complex and involve many cell types, making it extremely difficult to predict which gene products are reliable makers for alloimmune response or allograft rejection. DNA microarray analysis of genes expressed in peripheral lymphocytes during human renal allograft immune response and in highly sensitized patients has not been reported previously.In this study, we sequentially investigated early and late gene expression profile of peripheral lymphocytes in human renal allograft recipients in the early post transplantation period (24 hours late and 7 days late) by means high-density cDNA microarray containing 4096 human genes (Part I and Part II). In these two parts, we also analyse the regulation of target genes expression by immunosuppressive agents including methylprednisolone pulse treatment and triple immunosuppressive medications consisting of cyclosporine, mycophenolate mofetil, and prednisone. In Part III, we comparatively analyze the immunological genes associated with sensitization of peripheral lymphocytes in highly sensitized patients using cDNA microarray technology.PartiGene expression profile analysis of peripheral lymphocytes in human renal allograftrecipients during early post-transplantation period using cDNA microarraytechnologyObjective: To explore differentially exp... |
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