Impact Of HLA Matching On PRA Formation Of Patients With Chronic Renal Allograft Dysfunction And It's Impact On One Year Outcome Of Presensitized Renal Allograft Recipients

Part OneIMPACT OF HLA MATCHING ON PRA FORMATION OF PATIENTS WITH CHRONIC RENAL ALLOGRAFT DYSFUNCTIONObjective To evaluate the effect of human leukocyte antigen(HLA) matching on panel reactive antibodies(PRA) formation in patients with chronic renal allografl dysfunction(CRAD).Methods PRA measurement and HLA matching have been carried out for the patients who received their first renal graft.For recipients who were not sensitized before transplantation,PRA measurement was carried out after the grafts dysfunctioned.PRA were demonstrated by enzyme-linked immunosorbent assay (ELISA) by means of LAT1240 for value and specificity.HLA of donors and recipients were measured by means of polymerase chain reaction with sequence specific primers(PCR-SSP).This study included 24 patients.The effect of HLA matching on PRA formation in these patients was analyzed.Results(1) There were 17 patients sensitized,compared to 7 patients unsensitized. Among the 17 sensitized patients,HLA-Ⅰantibodies,HLA-Ⅱantibodies and both two kinds of antibodies were found in 8,15 and 6 patients respectively.A1,A24,DR7, DR9,DR12 and DR13 antibodies were the most frequently found PRA.As to donor specific antibodies(DSA),A1,DR7 and DR9 antibodies were most frequently found. (2) The number of mismatched HLA-Ⅰantigens compared by 6-antigen matching (Ag M) standard was of no statistical differenc(P＞0.05) between HLA-Ⅰantibody positive and negative group,compared to being of statistical difference(P＜0.01) between these two groups compared by cross reactive group(CREG) matching standard.The number of mismatched HLA-Ⅱantigens between HLA-Ⅱantibody positive and negative group was of statistical difference compared by Ag M standard (P＜0.05) or amino acid residue matching(Res M) standard(P＜0.01).(3) Most frequently found donor HLA antigen A2 and A30 did not cause formation of A2 and A30 antibodies in recipients.Both 2 cases of donor A1 to recipient A2 antigen mismatch has caused formation of A1 antibody,the DSA to the donor A1 antigen. And mismatch of donor antigen DR7 and DR9 has caused more formation of DSA than others as well.Conclusions(1) HLA mismatch is an important cause of sensitization in patients with CRAD.(2) Better HLA matching of preceding renal transplant may decrease the occurrence of sensitization rate in patients waiting for retransplantation.(3) Mismatch of certain HLA antigen,such as A1,DR7 and DR9,is more likely to cause the formation of PRA in kidney recipients. Part TwoIMPACT OF HLA MATCHING AND RECIPIENT'S PRA ON ONE YEAR OUTCOME OF PRESENSITIZED RENAL ALLOGRAFT RECIPIENTSObjective To evaluate the impact of HLA matching and Recipicnt's PRA on one year outcome in of prcsensitized renal allografi recipients.Methods In the 73 sensitized uremia recipients,we determined percentage of panel reactivity and the specificity of anti-HLA-Ig G antibodies.HLA genotyping was performed by PCR with sequence-specific primers(PCR-SSP).We analyzed which factors influence the early graft outcome,including HLA mismatching,class and degree of panel reactivity,target antigen of donors,as compared to the 81 unscnsitizcd recipients(the control group).Results(1) The early rejection rate was 35.6%in sensitized recipients and 18.5%in unsensitized recipients,with statistical significance(P＜0.05).The 1-year survival rate of the graft in the sensitized and unsensitizcd group was 80.8%and 95.1%respectively,with statistical significance(P=0.01).(2) The number of HLA mismatched alleles,including HLA-Ⅰand HLA-Ⅱ,were assessed in sensitized recipients between the rejection group and non-rejection group either with Ag M or Res M.No statistical significance was found,as the same between the 1-year graft survival group and loss group.(3) Compared to the control group,recipients with both PRAⅠandⅡantibodies(n=23) had a significantly higher rejection rate and lower survival rate of the graft(P＜0.01).The rejection rate of the recipients with a peak PRA＞50%(n=12) was significantly higher than the control group,while survival rates of both the recipients with peak PRA≤50%(n=61) and those＞50%(n=4) were found significantly lower than the control group(P＜0.05%);the rejection rate of those with pretransplant PRA＞50%(n=4) was significantly higher than the control group and those with peak PRA≤50%(P＜0.05),while survival rates of both those with pretransplant peak PRA＞50%and those≤50%(n=69) were found lower than the control group(P＜0.05%).(4) The rejection rate of target antigen positive group (n=13) increased.The difference was significant compared to control group,the target antigen negative group,and the peak target antigen group(n=8),respectively (P＜0.01,0.01 and 0.05);1-year graft survival rate of target antigen positive group was significantly lower than that of the control group(P＜0.05);both rejection rate and 1-year survival rate of target antigen unknown group(n=7) were found insignificant compared to the target antigen positive group.Compared to the control group or the negative group,the graft rejection in the HLA-Ⅰtarget antigen positive group was significantly higher(P＜0.01) and survival rate was lower(P＜0.01 and P＜0.05).No statistical significance was shown in the HLA-Ⅱtarget antigen positive group.(5)Recipients with pretransplant plasmapheresis(PP) or immunoadsorption(IA) had better graft effects postoperatively,which was significantly different with the control group(P＜0.01).(6) 3 cases of hyper reactive rejection(HR) occurred in recipients with 0-mismatches according to Res M.HR occurred in 3 out of the 5 cases with positive HLA-Ⅰtarget antigen,while 1 had functioning graft for 7 years.No HR was found in all the 8 cases with positive HLA-Ⅱtarget antigens,while 1 HR happened in the PRA-Ⅱpositive but target antigen unknown group.Conclusions(1) The number of HLA mismatched alleles has no significant impact on graft rejection or survival rate,as long as more than 2 mismatches exist.(2) 0 mismatching with Res M can not prevent HR in sensitized recipients.(3) Positive PRA screening has adverse effects on transplant outcomes,which is more evident when HLA-ⅠandⅡare dual positive.(4) Sensitization of recipients is reversely correlated with early graft outcome,worse when PRA＞50%.(5) Failures are more likely induced when donors possess target antigens for panel reactive antibodies, especially the HLA-Ⅰantigens.(6) Pretransplant antibody preparations such as PP improve the access of sensitized patients to DD organs and promote more equitable allocation to a highly disadvantaged group of patients waiting renal transplantation.(7) To avoid target antigen positive donors is the fundamental measure to prevent HR and early rejections.