肾移植交叉反应组配原则临床应用分析

目的探讨人类白细胞抗原(HLA)交叉反应组(CREGs)配型原则在临床肾移植中的应用及意义.方法对传统配型原则Ⅰ类抗原错配(MM)2个以上位点的149例肾移植,采用CREGs配型原则选择供受者,观察其术后一年存活率及术后一月内急性排斥反应发生率情况.结果 在不考虑DR位点的情况下, 按CREGs配型原则选择供受者,供受者HLA-Ⅰ类抗原0、1和2MM数分别为36例(24.16%),62例(41.61%)和51例(34.22%);术后一月内急性排斥反应发生率分别为16.67%(6例)、27.40%(16例)和43.14%(22例);术后一年存活率分别为97.22%(35例)、93.55%(58例)和 82.35%(42例).结论 在传统配型不满意的情况下,对HLA-Ⅰ类抗原采用CREGs配型原则选择供受者,可以获得满意的移植肾一年存活率,减少术后排斥反应发生率,为等待供肾的患者提供了更多机遇,同时亦为获得配型良好的供肾提供了机会.     

HLA氨基酸残基配型在免疫致敏受者肾移植中的应用探讨

[目的] 探讨人类白细胞抗原( HLA)氨基酸残基配型( Res M)在免疫致敏尤其是高敏受者肾脏移植中的临床意义.[方法] 对 47例致敏受者采用酶联免疫吸附法( ELISA)检测体内预存的群体反应性抗体-IgG( PRA-IgG)的水平及特异性;采用一步法单克隆抗体技术和微量序列特异性引物聚合酶链反应( Micro-PCR-SSP)技术进行 HLAⅠ类和Ⅱ类分型.[结果] 47例致敏受者的 PRA-IgG水平为 8.3%～ 96.4%,平均为 38.8%,供受者间按传统的 HLA抗原错配( MM)原则, 0-1错配( MM)、 2 MM的患者分别为 5例( 10.6 %)、 9例( 19.1%),而按 Res M的原则, 0-1 MM、 2 MM患者分别提高到 22例( 46.8%)、 17例( 36.1%)( P< 0.001);其中 PRA≥ 50%的 18例高敏受者中, 0-1MM 13例( 72.2%),而 PRA< 50%的 29例受者中, 0-1MM 9例( 31%),两者间差异有统计学意义( P< 0.001); 47致敏受者肾移植术后 3个月内排斥反应的发生率为 35%,在 18例 PRA≥ 50%的高敏受者中,仅有 4例( 22.2%)发生排斥反应, 29例 PRA< 50%的受者中, 11例( 37.9%)发生排斥反应 (P > 0.05).[结论] HLA氨基酸残基配型可显著提高供受者的相配率,良好的 HLA配型对减少高敏受者肾移植的排斥反应、提高移植物的存活率具有重要意义.     

149例肾移植交叉后反应组配型报道

目的：探讨人类白细胞抗原（HLA）交叉反应组（CREGs)配型原则在临床肾移植中的应用及意义。方法：应用单抗湿板法进行HLA－Ⅰ类抗原分型，对传统配型原则Ⅰ类抗原错配（MM）2个以上位点的149例肾移植，采用CREGs配型原则选择供受。观察其术后一年存活率及术后一月内急性排斥反应发生率情况。结果：在不考虑DR位点的情况下，按CREG s配型原则选择供受，供受HLA－Ⅰ类抗原0、1和2MM数分别为36例（16．67％），62例（41．61％）和51例（34．22％）；术后一月内急性排斥反应发生率分别为16．67％（6例）、27．40％（16例）和43．14％（22例）。术后一年存活率分别为97．22％（35例）、93．55％（58例）和82．35％（42例）。结论：在传统配型不满意的情况下，对HLA－Ⅰ类抗原采用CREGs配型原则选择供受，可以获得满意的移植肾一年存活率，减少术后排斥反应发生率，为等待供肾的患提供了更多机遇，同时亦为获得配型良好的供肾提供了机会。     

HLA分型筛选致敏肾移植受者疗效观察

目的：研究致敏受经人类白细胞抗原（HLA）配型及HLA交叉反应组（CREGs)配型后行肾移植的效果。方法：应用美国莱姆德细胞板检测受体的群体反应性抗体（PRA）；应用单抗湿板行受HLA-Ⅰ类抗原分型；微量序列特异性引物（Micro-SSP行HLA-Ⅱ类基因分型。结果：75例受PRA阳性率为11%-96%，平均48.5%;51例患术后1周内移植肾功能恢复正常，13例术后出现移植肾急性排斥反应（AR），经静脉点滴OKT3抗排斥，9例肾功能恢复正常，4例切除移植肾，11例患术后并发移植肾功能延迟恢复（DGF），9例患于术后2周至2个月移植肾功能逐渐恢复正常，75例患移植成功率93.3%。死亡率2.7%，总急性排斥率及总DGF发生率分别为17.3%和14.7%。按CREGs配型原则，供受CREGs的0、1、2个错配（MM）分别为13例（17.3%),44例（58.7%)和18例（24.0%)，3MM-6MM均为0，明显高于传统HLA抗原配型结果。结论：致敏受必须严格按照HLA配型及HLACREGs配型原则，对减少移植肾排斥反应，提高并延长移植肾的存活率有重要意义。     

标准HLA配型与氨基酸残基配型在再次肾移植中的应用

【目的】探讨人类白细胞抗原（HLA）配型（Ag M）和氨基酸残基配型（Res M）标准在再次肾移植受者中的应用。【方法】回顾性分析HLA配型、Res M及基因水平HLA-DR相容对78例再次肾移植患者早期肾功能、早期排斥反应及人/肾存活率的影响。【结果】应用Res M标准,0MM受者由AgM组2.6%提高到ResM组14.1%（P=0.0027）,0～1MM组受者由Ag M组15.4%提高到ResM组52.6%（P〈0.001）;残基相配组与残基错配组相比,DR相配组与DR错配组相比：早期移植肾功能恢复快、早期排斥反应发生率显著减少,1、3年移植肾存活率明显提高（P〈0.05）。【结论】HLA-Res M可大幅度增加供受者的相配概率,显著降低术后早期排斥反应发生率,适合在再次肾移植患者中应用。基因水平HLA-DR相容对再次肾移植术后早期排斥反应和存活率具有重要影响。     

组织配型对同种肾移植急性排斥反应的影响

目的：探讨组织配型与肾移植术后急性排斥反应的关系。方法分别采用补体依赖的淋巴细胞毒交叉试验筛选受者,采用ELISA方法检测受者群体反应抗体,比较分析传统HLA配型与交叉反应组（ CREGs ）配型两种配型方法肾移植术后急性排斥反应发生情况。结果109例肾移植患者中,补体依赖的交叉淋巴细胞毒试验均为阴性。群体反应抗体（PRA）阴性103例,其中7例（5.38％）发生AR;PRA阳性6例,其中3例（33.33％）发生AR。传统HLA配型0～6 MM分别占0.92％,2.75％,3.67％,22.02％,35.78％,28.44％和6.42％,相对应AR发生率分别为0、0、0、0、15.38％、9.68％和0;CREGs配型6 MM时无移植病例,CREGs配型0～5 MM分别占2.75％,8.26％,20.18％,39.45％,26.61％,2.75％,相对应AR发生率分别为0、0、4.55％、11.63％、10.34％和0。将0～4 MM组合并统计,传统HLA配型与CREGs 配型AR发生率相比较差异无统计学意义（χ2＝0.00,P＞0.05）;传统HLA配型与CREGs配型0～4 MM的比率差异有统计学意义（χ2＝36.80,P＜0.01）。结论术前PRA阳性者,AR发生率高于PRA阴性者。与传统HLA配型相比,CREGs配型能够提高受者和供者HLA匹配的概率。0～4 MM时传统HLA配型与CREGs配型对AR发生率无明显差别。     

HLA组织配型在PRA阳性受者肾移植中的应用

目的探讨人类白细胞抗原(HLA)组织配型在群体反应性抗体(PRA)高受者肾移植中的意义。方法对26例群体反应性抗体(PRA)高达38％～88％的肾功能衰竭患者用单克隆抗体分型板实施HLA组织配型。结果供受者HLA-A，B，DR位点各有一个抗原相配者5例；HLA-A位点1个抗原相配B位点1个抗原、DR位点2个抗原相配者8例；HLA-A位点2个抗原相配、B位点2个抗原相配、DR位点1个抗原相配者4例；HLA-A位点1个抗原相配、B位点2个抗原相配、DR位点2个抗原相配者9例。术后5例发生急性排斥反应，经抗排异治疗逆转4例，1例移植肾失功；25例肾功能恢复正常。结论良好的HLA配型对PRA高的受者的肾移植具有重要意义。     

标准HLA配型与氨基酸残基配型在再次肾移植中的应用

 【目的】探讨人类白细胞抗原（HLA）配型（Ag M）和氨基酸残基配型（Res M）标准在再次肾移植受者中的应用。【方法】回顾性分析HLA配型、Res M及基因水平HLA-DR相容对78例再次肾移植患者早期肾功能、早期排斥反应及人/肾存活率的影响。【结果】应用Res M标准,0MM受者由AgM组2.6%提高到ResM组14.1%（P=0.0027）,0～1MM组受者由Ag M组15.4%提高到ResM组52.6%（P〈0.001）;残基相配组与残基错配组相比,DR相配组与DR错配组相比：早期移植肾功能恢复快、早期排斥反应发生率显著减少,1、3年移植肾存活率明显提高（P〈0.05）。【结论】HLA-Res M可大幅度增加供受者的相配概率,显著降低术后早期排斥反应发生率,适合在再次肾移植患者中应用。基因水平HLA-DR相容对再次肾移植术后早期排斥反应和存活率具有重要影响。     

群体反应抗体、HLA交叉组误配率与肾移植术后早期排斥反应的关系

HLA配型及群体反应抗体的检测在肾移植中的作用越来越受到重视.本文作者选择本院近2年来肾移植患者230例,按美国国立器官共享联合网络中心(UNOS)制定的HLA交叉反应组(CREGs)配型原则,严格地进行供受者配型,研究供受者之间交叉反应组配型(PRA)与术后早期急性排斥反应的关系.     

HLA氨基酸残基配型标准在肾移植中的应用

目的 评价HLA氨基酸残基配型新标准在肾移植中的应用。方法 应用血清学和基因分型方法对134例肾移植供受者进行HLA-Ⅰ，Ⅱ类抗原分型，并比较氨基酸残基配型标准与传统的HLA六抗原无错配标准的关系。结果 HLOA氨基酸残基配型标准可以提高肾移植供受者的相配率，六抗原无错配率可由0.75%提高到2.24%，六抗原安全错配的几率由15.67%降至2.24%。结论 HLA氨基酸残基配型标准是一种更为实用的同种异体移植配型策略。     

PRA配型技术在致敏受者肾移植术中的应用研究

目的 探讨群体反应性抗体(PRA)配型技术在致敏受者肾移植中的临床效果.方法 应用抗原板(LAT),采用酶联免疫吸附法(ELISA)检测肾移植受者术前的PRA;采用PRA配型技术进行术前配型.结果 12例致敏受者组采用PRA配型技术,肾移植术后肾功能恢复正常,无1例发生超急性排斥反应,术后1个月内急性排斥反应的发生率为25%;同期43例非致敏受者组,术后1个月内急性排斥反应的发生率为18.6%,虽较致敏受者组低,但两组之间差异无统计学意义.结论 PRA配型技术对减少致敏受者肾移植排斥反应,提高移植物存活率具有重要意义.     

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.     

Protein A immunoadsorption combined with rituximab in highly sensitized kidney transplant recipients

Background The number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure. The present study aimed to investigate the safety and efficacy of protein A immunoadsorption combined with rituximab （RTX） in highly sensitized recipients of kidney transplants.
Methods Seven highly sensitized recipients of living-related renal transplants （4 men and 3 women, mean aged 42.5 years old （range 33-51）） were pretreated with this combination. Human leukocyte antigen （HLA） mismatch number was 2-5. Panel reactive antibody （PRA） of class Ⅰwas high in 2 cases and that of class Ⅱwas high in 1 case. All patients were pretreated with immunoadsorption 2-10 times. Immunoglobulin and PRA changes were monitored before and after absorption. The operation was conducted when PRA or immunoglobulin levels were at or below normal levels. Immunosuppressive drugs were provided 3-5 days before the operation, and one dose of RTX （375 mg/m^2） was infused with polyclonal antibody on the day of operation. Postoperative creatinine （Cr）, creatinine clearance rate （Ccr）, PRA ratio, and immunoglobulin changes were monitored.
Results All 7 patients had good recovery without delayed graft function. Acute rejection occurred in 3 cases at postoperative days 8, 10, and 14, respectively. The Banff 07 biopsy grades were la in 1 case and lla C4d0 in 2 cases. Successful reversion was achieved after giving methylprednisolone or antithymocyte immunoglobulin ＋ cyclophosphamide. All patients were discharged with normal renal function, mean class Ⅰ PRA was 14% and mean class ⅡPRA was 35%. PRA was completely negative in 3 cases.
Conclusion Protein A immunoadsorption combined with RTX can safely reduce the occurrence of humoral rejection in highly sensitized renal transplant recipients.     

致敏受者肾移植急性排斥反应的影响因素

目的 探讨致敏受者肾移植急性排斥反应的影响因素。方法 对102例术前致敏患者临床资料进行回顾性分析,探讨群体反应抗体(PRA)水平、氨基酸残基配型、术后PRA水平升高及细胞因子基因型对急性排斥反应发生率的影响。结果和结论 102例致敏肾移植受者术后随访期间发生急性排斥反应33例次,其中PRA水平、氨基酸残基相配程度、术后PRA水平升高、TNF-α高产量基因型和IL-10高产量基因型对移植肾的急性排斥发生率均有显著性影响。术前综合评估这些因素,有利于制订合理的免疫抑制方案。     

致敏受者肾移植急性排斥反应的影响因素

目的：探讨致敏受者肾移植急性排斥反应的影响因素。方法：对102例术前致敏患者临床资料进行回顾性分析．探讨群体反应抗体(PRA)水平、氨基酸残基配型、术后PRA水平升高及细胞因子基因型对急性排斥反应发生率的影响。结果和结论：102例致敏肾移植受者术后随访期间发生急性排斥反应33例次，其中PRA水平、氨基酸残基相配程度、术后PRA水平升高、TNF-α高产量基因型和IL-10高产量基因型对移植肾的急性排斥发生率均有显著性影响。术前综合评估这些因素，有利于制订合理的免疫抑制方案。     

Expression characteristics of major histocompatibility complex class I-related chain A antibodies and immunoadsorption effect in sensitized recipients of kidney transplantation

Background  Sensitized recipients have a high risk of immunological graft loss due to hyperacute rejection and/or accelerated acute rejection. The presence of major histocompatibility complex class I-related chain A (MICA) antibodies has also been described associated with an increased rate of kidney-allograft rejection. The aim of this study was to describe the expression of MICA antibodies in sensitized recipients of renal transplantation and evaluate its influence on the kidney transplantation recipients.

Methods  A total of 29 sensitized recipients were included in this study. All patients received the MICA antibodies detection before and after protein A immunoadsorption. Panel reactive antibody (PRA), HLA-matches, acute rejection and postoperative one to four-week serum creatinine level were also collected and analyzed, respectively. No prisoners were used in this study.

Results  Eight patients (27.6%) in all 29 sensitized recipients expressed the MICA antibodies but did not show higher acute rejection rate than the non-expressed patients (3/8, 37.5% vs. 8/21, 38.1%; P=1.000). Recipients with PRA >40% showed higher expression levels of MICA antibodies than the recipients with PRA <40% (7/16, 43.8% vs. 1/13, 8.3%; P=0.044). HLA mismatch did not have any effect on the expression of MICA antibodies (P=1.000). MICA antibodies positive group had higher serum creatinine level than the control in postoperative one week ((135.4±21.4) µmol/L vs. (108.6±31.6) µmol/L, P=0.036), but no significant difference in postoperative four weeks ((89.0±17.1) µmol/L vs. (77.1±15.9) µmol/L, P=0.089). MICA antibodies decreased significantly after protein A immunoadsorption.

Conclusions  MICA antibodies increase in the sensitized recipients, which have significant effects on the function of allograft in early postoperative period. Protein A immunoadsorption can decrease MICA antibodies effectively in sensitized recipients.

     

氨基酸残基配型策略在高致敏尿毒症患者肾移植中的应用研究

目的：探讨人类白细胞抗原（HLA）氨基酸残基配型（ResM）标准在高致敏尿毒症患者肾移植中的应用。方法：在动态监测群体反应性抗体（PRA）水平、特异性及淋巴毒交叉配合试验的基础上,采用ResM标准选取与供者最匹配的供体。结果：56例尿毒症患者术前PRA均大于20％,采用Terasaki提出的ResM标准,供受者0抗原错配（MM）为6例（10．7％）,IMM为13例（23．2％）,2MM为19例（33．9％）,3MM为13例（23．2%）,4MM为5例（9．1%）,5MM和6MM为0例。术后56例受者均未发生超急性排斥反应,17例（30．4％）发生急性排斥,经甲基强的松龙冲击治疗后3例（5．4％）切除移植肾,另14例（25％）排斥反应逆转,肾功能恢复。5例（8．9％）发生移植物功能延迟恢复（DelayGraftFunction,DGF）,经血液透析过渡治疗后均在5周内恢复。结论：ResM标准可提高PRA阳性受者与供者之间HLA相配程度,缩短患者等肾时间,降低排斥反应的发生率,是一种有效的、具有临床实用价值的配型策略。     

The importance of PRA detection and PRA clearance in cadaveric renal transplantation

Though complement-dependent cytototicity (CDC)asSay is widely adopted as a standald histocompatibilitytest before haplantalon in most of the transplantationcenters in our countw, it yields unacceptably high ~ ofhypemeute rejechon (HR) Of the allograft because of itslow sensihvity[']. In some cases, even the new powerful~nosuPPressants fail to suPPress the disastIDus edejection (GR). In this stUdy, we examined the validity.Of Panel reactive antibodies (PRA) measmnt as a pretranSPlant h…     

群体反应性抗体技术及HLA配型在1700例肾移植中的应用研究

OBJECTIVE: To evaluate the role of panel reactive antibody (PRA) screening and human leukocyte antigen (HLA) typing in renal transplantation. METHODS: PRA screening and HLA typing were performed in 1 700 patients eligible for the first group of renal transplantation who had 3 to 6 HLA matches in HLA-A, B and DR with the donor, and in cases positive for PRA, plasma exchange was conducted. Another 423 patients who did not receive PRA screening or HLA typing constituted the second group. The changes of immune variables, incidences of acute rejection and the effect of HLA-A, B, DR matching on long-term graft survival were observed. RESULTS: In 1 700 cases of group 1, post-transplantation CsA dose was reduced to 5 to 7 mg*kg(-1)*d(-1) and the graft function recovery time ranged from 2 to 16 d, averaging 5 d. Acute graft rejection occurred in 252 (14.8%) cases, but no hyper-acute rejection was observed. The 1-, 3- and 5-year patient/graft survival rates were 98.6%/96.7%, 93.1%/87.3% and 88.1%/83.6% respectively. In group 2, CsA dose ranged from 8 to 12 mg*kg(-1)*d(-1) and the graft function recovery time was 4 to 30 d, averaging 13 d. Hyper-acute rejection occurred in 9 (2.1%) and acute rejection in 198 (46.8%) cases, and the 1-, 3- and 5-year patient/graft survival rates were 86.7%/76.3%, 72.5%/67.9% and 69.5%/59.3% respectively. CONCLUSIONS: Negative PRA and good HLA matching can eliminate the incidences of hyper-acute rejection, decrease the rate of acute rejection and improve both patient and graft survival rates.