Impact of human leukocyte antigen matching and recipients′ panel reactive antibodies on two-year outcome in presensitized renal allograft recipients

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.

Impact of human leukocyte antigen matching and recipients' panel reactive antibodies on two-year outcome in presensitized renal allograft recipients

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 P=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. Presensitizedrecipients 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.