BACKGROUND Chronic kidney disease is associated with immunological disorders,presented as phenotypic alterations of T lymphocytes.These changes are expected to be restored after a successful renal transplantation;howe...BACKGROUND Chronic kidney disease is associated with immunological disorders,presented as phenotypic alterations of T lymphocytes.These changes are expected to be restored after a successful renal transplantation;however,additional parameters may contribute to this process.AIM To evaluate the impact of positive panel reactive antibodies(PRAs)on the restoration of T cell phenotype,after renal transplantation.METHODS CD4CD28null,CD8CD28null,natural killer cells(NKs),and regulatory T cells(Tregs)were estimated by flow cytometry at T0,T3,and T6 which were the time of transplantation,and 3-and 6-mo follow-up,respectively.Changes were estimated regarding the presence or absence of PRAs.RESULTS Patients were classified in two groups:PRA(-)(n=43)and PRA(+)(n=28)groups.Lymphocyte and their subtypes were similar between the two groups at T0,whereas their percentage was increased at T3 in PRA(-)compared to PRA(+)[23(10.9-47.9)vs 16.4(7.5-36.8)μ/L,respectively;P=0.03].Lymphocyte changes in PRA(-)patients included a significant increase in CD4 cells(P<0.0001),CD8 cells(P<0.0001),and Tregs(P<0.0001),and a reduction of NKs(P<0.0001).PRA(+)patients showed an increase in CD4(P=0.008)and CD8(P=0.0001),and a reduction in NKs(P=0.07).CD4CD28null and CD8CD28null cells,although initially reduced in both groups,were stabilized thereafter.CONCLUSION Our study described important differences in the immune response between PRA(+)and PRA(-)patients with changes in lymphocytes and lymphocyte subpopulations.PRA(+)patients seemed to have a worse immune profile after 6 mo follow-up,regardless of renal function.展开更多
Background Renal transplantation in sensitized candidates remains a highly significant challenge worldwide. The production of panel reactive antibody （PRA） against human leukocyte antigen （HLA） is a major risk fac...Background Renal transplantation in sensitized candidates remains a highly significant challenge worldwide. The production of panel reactive antibody （PRA） against human leukocyte antigen （HLA） is a major risk factor in presensitized recipients. The aim of this study was to evaluate the impact of HLA matching and recipients＇ PRA on two-year outcome in presensitized renal allograft recipients. Methods We determined the percentage of panel reactivity and specificity of anti-HLA immunoglobulin （Ig） G antibodies in 73 presensitized renal allograft recipients compared with 81 unsensitized recipients （control group）. HLA genotyping of both recipients and corresponding donors was performed by PCR with sequence-specific primers （PCR-SSP）. We analyzed the factors influencing the early graft outcome （two-year rejection rates and survival rates of the grafts）, including HLA mismatching, class and degree of panel reactivity, and target antigen of donors. Results Presensitized recipients had a worse two-year outcome than unsensitized recipients （P=0.019 for rejection rate, P=0.01 for survival rate）. The difference in number of HLA-mismatched alleles with either 6-antigen matching （Ag M） standard or amino acid residue matching （Res M） standard was not significant between the rejection and non-rejection groups of presensitized recipients or between the graft survival group and graft loss group. Compared with the control group, recipients with both PRA-I and PRA-II antibodies had a significantly worse two-year outcome （P=0.001 for rejection rate, P=0.002 for survival rate）. The two-year outcomes of the peak PRA 〉50% group and its subgroup, at-transplant PRA 〉50% group, were significantly worse compared with the control group （P=0.025 and P=0.001 for rejection rate, P=0.043 and P=0.024 for survival rate）. The rejection rates of the at-transplant target antigen positive group and its subgroup, HLA-I target antigen positive group, were significantly higher than the control group （P=0.001 and P=-0.001）, target antigen negative group （P=0.003 and P=0.001）, and peak target antigen positive with negative at-transplant target antigen group （P=0.024 and ,0=-0.002）. Two-year graft survival rates of the target antigen positive group and HLA-I target antigen positive group were significantly lower than the control group （P=0.012 and ,P=0.001）. The two-year outcome of target antigen unknown group was similar to that of the target antigen positive group. Presensitized recipients with pre-transplant plasmapheresis or immunoadsorption （PRA prepared group） had a better but non-significant two-year outcome than the control group. However, the PRA unprepared presensitized recipients were different to the control group （P=-0.004 for rejection rate and P=-0.005 for survival rate）. Hyperacute rejection （HR） occurred in three recipients with positive HLA-I target antigen and without mismatch according to Res M and in one case with positive PRA-II （for an unknown target antigen）. No HR occurred in eight cases with positive HLA-II target antigens. Conclusions Pre-transplant PRA preparations might improve the access of presensitized patients to renal donors. Avoiding antigen-positive donors remains a fundamental measure in preventing HR and early rejections.展开更多
Our understanding of transplant immunology has advanced from gross allograft rejection to cellular response and to current molecular level. More sensitive assays have been developed to characterize patient sensitizati...Our understanding of transplant immunology has advanced from gross allograft rejection to cellular response and to current molecular level. More sensitive assays have been developed to characterize patient sensitization and to detect pre-existing donor-specific antibodies(DSA) in pre-transplant crossmatch. After a transplant, pre-existing or de novo DSA are increasingly monitored to guide clinical management. Therefore, it is important for clinicians to understand the basic concepts and key components of transplant immunology as well as be familiarized with the modern immunological techniques used in kidney transplantation.展开更多
Objective: To evaluate the short- and long-term effects of panel reactive antibody (PRA) examination and PRA clearance on the patient/kidney survival after cadaveric renal transplantation. Method: We reviewed the reco...Objective: To evaluate the short- and long-term effects of panel reactive antibody (PRA) examination and PRA clearance on the patient/kidney survival after cadaveric renal transplantation. Method: We reviewed the records of 1 277 patients who underwent cadaveric renal transplantation with good human leukocyte antigen (HLA) matching with the donors from 1978 to 1998. Four hundred and twenty-three patients underwent renal transplantation from 1978 to 1990 without PRA examination made up the first group. The other 854 patients with PRA level examination before the operation from 1991 to 1998 were regarded as the second group. Preoperative plasmaphereses were performed for those with PM levels higher than 30%. The episodes of hyperacute rejection, acute rejection and l-, 3- and 5-year patient/graft survival rate were evaluated. To rule out the interference of different immunosuppressants, we made a comparative study between the recipients with uncorrectable high PRA levels (> 20% ) in the second group and those with reduced PRA levels (< 10% ) by plasmaphere- sis. Results: In the first group, 9 (2.l%) hyperacute rejection and 198 (47%) acute rejection occurred The 1-, 3- and 5-year patient/graft survival rates were 86. 7%/76. 3%, 72. 5%/67. 9% and 87 .0%/81. 6%, respectively. In the second group, no hyperacute rejection happened and acute rejection was occurred in 162 cases (19.0% ), and the l-, 3- and 5year patient/graft survival rates were 97. 3%/95.0%, 92%/84. 2% and 87.0%/81 .6%, much lower than that in the first group. Of the 49 recipients with high PRA levels, 33 had PRA levels below 10% after plasmapheresis, who had a lower incidence of ocute rejection, a higher rate of rejection reversal and a higher graft survival rate at 1, 3 and 5 years than the rest 16 cases (PRA > 20% after plasmapheresis). Conclusion: The PRA level examination and PRA clearance are important for the success of renal transplantation. They help eradicate the hyperacute rejection, reduce the risk of acute rejection and improve patient and graft survival.展开更多
文摘BACKGROUND Chronic kidney disease is associated with immunological disorders,presented as phenotypic alterations of T lymphocytes.These changes are expected to be restored after a successful renal transplantation;however,additional parameters may contribute to this process.AIM To evaluate the impact of positive panel reactive antibodies(PRAs)on the restoration of T cell phenotype,after renal transplantation.METHODS CD4CD28null,CD8CD28null,natural killer cells(NKs),and regulatory T cells(Tregs)were estimated by flow cytometry at T0,T3,and T6 which were the time of transplantation,and 3-and 6-mo follow-up,respectively.Changes were estimated regarding the presence or absence of PRAs.RESULTS Patients were classified in two groups:PRA(-)(n=43)and PRA(+)(n=28)groups.Lymphocyte and their subtypes were similar between the two groups at T0,whereas their percentage was increased at T3 in PRA(-)compared to PRA(+)[23(10.9-47.9)vs 16.4(7.5-36.8)μ/L,respectively;P=0.03].Lymphocyte changes in PRA(-)patients included a significant increase in CD4 cells(P<0.0001),CD8 cells(P<0.0001),and Tregs(P<0.0001),and a reduction of NKs(P<0.0001).PRA(+)patients showed an increase in CD4(P=0.008)and CD8(P=0.0001),and a reduction in NKs(P=0.07).CD4CD28null and CD8CD28null cells,although initially reduced in both groups,were stabilized thereafter.CONCLUSION Our study described important differences in the immune response between PRA(+)and PRA(-)patients with changes in lymphocytes and lymphocyte subpopulations.PRA(+)patients seemed to have a worse immune profile after 6 mo follow-up,regardless of renal function.
文摘Background Renal transplantation in sensitized candidates remains a highly significant challenge worldwide. The production of panel reactive antibody （PRA） against human leukocyte antigen （HLA） is a major risk factor in presensitized recipients. The aim of this study was to evaluate the impact of HLA matching and recipients＇ PRA on two-year outcome in presensitized renal allograft recipients. Methods We determined the percentage of panel reactivity and specificity of anti-HLA immunoglobulin （Ig） G antibodies in 73 presensitized renal allograft recipients compared with 81 unsensitized recipients （control group）. HLA genotyping of both recipients and corresponding donors was performed by PCR with sequence-specific primers （PCR-SSP）. We analyzed the factors influencing the early graft outcome （two-year rejection rates and survival rates of the grafts）, including HLA mismatching, class and degree of panel reactivity, and target antigen of donors. Results Presensitized recipients had a worse two-year outcome than unsensitized recipients （P=0.019 for rejection rate, P=0.01 for survival rate）. The difference in number of HLA-mismatched alleles with either 6-antigen matching （Ag M） standard or amino acid residue matching （Res M） standard was not significant between the rejection and non-rejection groups of presensitized recipients or between the graft survival group and graft loss group. Compared with the control group, recipients with both PRA-I and PRA-II antibodies had a significantly worse two-year outcome （P=0.001 for rejection rate, P=0.002 for survival rate）. The two-year outcomes of the peak PRA 〉50% group and its subgroup, at-transplant PRA 〉50% group, were significantly worse compared with the control group （P=0.025 and P=0.001 for rejection rate, P=0.043 and P=0.024 for survival rate）. The rejection rates of the at-transplant target antigen positive group and its subgroup, HLA-I target antigen positive group, were significantly higher than the control group （P=0.001 and P=-0.001）, target antigen negative group （P=0.003 and P=0.001）, and peak target antigen positive with negative at-transplant target antigen group （P=0.024 and ,0=-0.002）. Two-year graft survival rates of the target antigen positive group and HLA-I target antigen positive group were significantly lower than the control group （P=0.012 and ,P=0.001）. The two-year outcome of target antigen unknown group was similar to that of the target antigen positive group. Presensitized recipients with pre-transplant plasmapheresis or immunoadsorption （PRA prepared group） had a better but non-significant two-year outcome than the control group. However, the PRA unprepared presensitized recipients were different to the control group （P=-0.004 for rejection rate and P=-0.005 for survival rate）. Hyperacute rejection （HR） occurred in three recipients with positive HLA-I target antigen and without mismatch according to Res M and in one case with positive PRA-II （for an unknown target antigen）. No HR occurred in eight cases with positive HLA-II target antigens. Conclusions Pre-transplant PRA preparations might improve the access of presensitized patients to renal donors. Avoiding antigen-positive donors remains a fundamental measure in preventing HR and early rejections.
文摘Our understanding of transplant immunology has advanced from gross allograft rejection to cellular response and to current molecular level. More sensitive assays have been developed to characterize patient sensitization and to detect pre-existing donor-specific antibodies(DSA) in pre-transplant crossmatch. After a transplant, pre-existing or de novo DSA are increasingly monitored to guide clinical management. Therefore, it is important for clinicians to understand the basic concepts and key components of transplant immunology as well as be familiarized with the modern immunological techniques used in kidney transplantation.
文摘Objective: To evaluate the short- and long-term effects of panel reactive antibody (PRA) examination and PRA clearance on the patient/kidney survival after cadaveric renal transplantation. Method: We reviewed the records of 1 277 patients who underwent cadaveric renal transplantation with good human leukocyte antigen (HLA) matching with the donors from 1978 to 1998. Four hundred and twenty-three patients underwent renal transplantation from 1978 to 1990 without PRA examination made up the first group. The other 854 patients with PRA level examination before the operation from 1991 to 1998 were regarded as the second group. Preoperative plasmaphereses were performed for those with PM levels higher than 30%. The episodes of hyperacute rejection, acute rejection and l-, 3- and 5-year patient/graft survival rate were evaluated. To rule out the interference of different immunosuppressants, we made a comparative study between the recipients with uncorrectable high PRA levels (> 20% ) in the second group and those with reduced PRA levels (< 10% ) by plasmaphere- sis. Results: In the first group, 9 (2.l%) hyperacute rejection and 198 (47%) acute rejection occurred The 1-, 3- and 5-year patient/graft survival rates were 86. 7%/76. 3%, 72. 5%/67. 9% and 87 .0%/81. 6%, respectively. In the second group, no hyperacute rejection happened and acute rejection was occurred in 162 cases (19.0% ), and the l-, 3- and 5year patient/graft survival rates were 97. 3%/95.0%, 92%/84. 2% and 87.0%/81 .6%, much lower than that in the first group. Of the 49 recipients with high PRA levels, 33 had PRA levels below 10% after plasmapheresis, who had a lower incidence of ocute rejection, a higher rate of rejection reversal and a higher graft survival rate at 1, 3 and 5 years than the rest 16 cases (PRA > 20% after plasmapheresis). Conclusion: The PRA level examination and PRA clearance are important for the success of renal transplantation. They help eradicate the hyperacute rejection, reduce the risk of acute rejection and improve patient and graft survival.
