Clinical Investigation Of Effect Of HLA And MICA Antibodies On Chronic Allograft Rejection After Renal Transplantation

The incidence of acute rejection and allograft failure during short-term period after kidney transplantation has been greatly reduced by the application of new immunosuppressive agents and better HLA matching technology.One-year survival rate of cadaveric kidney transplantation has exceeded 90.0%.The clinical outcome of living donor kidney transplantation is even better.But the long-term outcome is not so satisfying.Graft rejection is still a serious problem,especially chronic rejection. Chronic rejection usually result in progressive loss of renal function,the reason remains unclear.Graft rejection is usually considered to be mediated by T lymphocytes,but recent studies have shown that humoral immuniny played an important role.The alloantibodies are created after sensitizing events such as a blood transfusion,a pregnancy,or an organ transplant.The alloantibodies can cause hyperacute rejection,acute rejection,chronic rejection and impact graft survival.The HLA mis-match is considered as the main reason for alloantibodies.HLA typing has become one of the most fundamental means of preventing graft rejection.However,graft rejection also occur in some HLA well-match recipients. MICA belongs to a multicopy gene family located in the major histocompatibility complex(MHC) class I region near the HLA-B gene.Its composition,expression,and the product category are different from the HLA-I genes.Much research has shown that antibodies against MICA antigens have a specific relevance with graft rejection. That MICA is expressed on the cell surface of endothelial cells and that HLA-related antigens have a polymorphic nature suggests that MICA-specific antibodies in the sera of transplanted patients could respond against MICA expressed by cells in the allograft.This issue is to explore the impact of anti-HLA and MICA antibodis on chronic renal rejection and long-term graft survival by monitoring renal transplant recipients' humoral immune status before and after transplantation.Objective:To investigate the effect of anti-HLA and MICA antibodies on chronic allograft rejection and long-term survival,and evaluate the meaning of dynamic monitoring of anti-HLA and MICA antibodies before and after transplantation with reducing the occurrence of chronic allograft rejection and improving the allograft survival.Methods:The 34 patients diagnosed with chronic allograft rejection were investigated as CR group,and over the same period the other 26 patients with good renal function were selected as control group.All the recipients' PRA was measured once before transplantation,and re-measured from January to July 2007 using One Lambda antigen tray(LAT).Anti-MICA antibodies were detected by Luminex and flow cytometric techologies.Results:1) Twenty seven(45%)of sixty patients were antibodies negative,and the other 33 (55%) were positive.12 patients were anti-HLA antibodies positive,14 patients were anti-MICA antibodies positive,seven patients were both antibodies positive. The CR group's anti-HLA antibodies positive rates were significantly higher than that in the control group(χ~2=8.591,P=0.003).2) The anti-MICA antibodies positive rates of patients in CR group and control groups were 47.1%and 19.2%,respectively.Also,The positive rate in the CR group was significantly higher than that in the control group(χ~2=5.015,P= 0.025).3) The serum creatine level of the patients with antibodies were significantly higher than those without antibodies.A worse graft function was evidenced in patients with HLA and MICA antibodies than those with only HLA or MICA antibody by serum creatine level.Conclusions:1) The emergence of anti-HLA antibody has a close relationship with chronic allograft rejection posttransplantation.Humoral immunity is a key factor in the development of chronic allograft rejection.2) There was a significant correlation between anti-MICA antibody and chronic allograft rejection.A worse graft survival was evidenced in patients with HLA and MICA antibodies.3) Dynamic monitoring of anti-HLA and MICA antibodies in recipients before and after transplantation may help to reduce the the the occurrence of chronic allograft rejection and improve the allograft survival.