The Experimental And Clinical Study On Transplantation Of High Sensitized Patients

Allograft rejection is a key problem which affected the survival time of grafts in organ transplantation. High panel rereactive antibody (PRA) patients who are highly sensitized to HLA antigens often have poor outcome after transplantation. The incidence of rejection after transplantation was obviously higher in the sensitized recipients and the graft survival rate was lower. The causes that make PRA higher were transfusion,pregnancy and retransplantation. With the progressive development of organ transplantation, the number of high sensitized patients increased greatly. The waiting time was longer, and some of them lost the opportunity of transplantation. To deal with them and make them receive compatible graft is a worldwide problem. By now there were some methods to decrease the PRA and make the recipients undergo organ transplantation, include plasmapheresis, immunoadsorption, well HLA typing, IVIG treatment, and so on. Part I The role of HLA typing and PRA in renal transplantation1. HLA typing of 573 were analyzed to observe the regulation of A, B, DR antigen distribution. To evaluate the HLA typing and GREG of the renal transplant recipients to select the appropriate donors. Result: The higher frequency of occurrence of HLA antigen are A2, A11, A24, B60(40), B13, DR15, DR51 , DR52 , DR53, DR 4, and the recipients with these antigens have more opportunity to gain well HLA matching. The proportion of 0, 1, 2, 3, 4, 5, 6 MM was0.78%, 1.56%, 5.06%, 10.12%, 27.63%, 29.96%|P 24.9%, respectively. But by CREG the proportion was 3.89%, 6.23%, 17.51%, 33.85%, 19.84%, 13.23%, 5.45%. There were no difference between HLA typing and CREG in the incidence of acute rejection and graft survival time.2. ELISA was used to detect the anti-HLA antibodies in renal recipients and to analyse the relationship between the levels of anti-HLA antibodies and sex, time of dialysis, transfusion, pregnancy, transplantation. Single factor analysis showed that the sex, transplantation, transfusionand pregnancy were the risk factors of sensitization(P<0.05). These factors could cooperate with each other and make the PRA level higher. The distribution of PRA antigens were not consistent with HLA antigens and the higher frequency of occurrence of PRA antigens are anti-A2 -, A11, A24, B60, B51, DR15, DR4.3. In organ transplantation, the grafts must be carefully monitored, but it is often difficult to make a quick and accurate diagnosis of unusual changes. The expression of CD 15s on peripheral lymphocytes was examined using flow cytometry in renal transplant recipients with rejection, without rejection, renal failure patients with high PRA and negative PRA, recipients with ATN, and healthy volunteers. There was a linear regression between the expression of CD 15s and the relative average fluorescent intensity. CD 15s was strongly expressed in all patients with rejection, but was not expressed in any of the patients without rejection or in any healthy volunteers, and when rejection was reversed, the expression of CD 15s returned to nomal. The detection of CD 15s on the peripheral lymphocytes by flow cytometry was an easy, helpful, and noninvasive means for the diagnosis of patients with elevated creatinine after renal transplantation. Part II The effect of immunoregulation of IVIG and the influence to the high sensitized patientsMore recently, some autoimmune disorders have been treated with high concentrations of FVIG and the results have been encouraging. The surprising key player that mediates the therapeutic benefits of IVIG is the Fc inhibitory receptor for IgG, FcRIIb, and the balance between it and activating Fc receptor FcRIIa. Under normal conditions FcyRIIa was mainly detected in macrophages/monocytes and B lymphocyte cells while FcyRIIb could not be detected. After IVIG administration, the expression of FcRIIb on the surface of U937 cells was rapid up-regulated(RT-PCR). FACS analysis of FcyRIIb expression on U937 and human peripheral blood mononuclear cells (PBM) after IVIG induction also showed more expression...