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。     

高敏受者肾移植术前行血浆置换的临床探讨

目的 :探讨高敏受者肾移植术前行血浆置换 (PE)的效果。方法 :12例高敏受者在肾移植术前进行PE治疗 ,37例高敏受者未行PE治疗 ,观察两组肾移植病人排斥反应发生率的差异。结果 :PE组置换前PRA值71.0 %± 19.1% ,置换后 34.3%± 17.9% ,两者有显著性差异 (P <0 .0 1)。术后发生超排 2例 ,急性排斥 2例 ;未行PE组发生超排 2例 ,急性排斥 8例 ,两组间超排和急性排斥的发生率均无显著性差异。结论 :PE对预防超排和降低急性排斥的发生率均无明显作用。PE治疗的主要适应症为PRA大于 80 %的受者 ,能快速降低PRA值 ,有助于HLA抗体特异性分析和HLA配型。     

肾移植中群体反应性抗体检测及高群体反应性抗体的临床对策

目的:研究群体反应性抗体在肾移植中的意义及对高群体反应性抗体受者的临床处理。方法:监测544例次肾移植受者的群体反应性抗体(PRA),并对PRA值≥40%的14例患者行血浆置换。结果:肾移植受者中,PRA阳性116例(21.3%),其中PRA≥40%26例;PPA阳性组排斥反应发生率(25.0%)高于PRA阴性组(4.9%),术后PRA水平升高组排斥反应发生率高于PRA无变化组,血浆置换组与未行血浆置换组排斥反应发生率无差异。结论:PRA的水平是评价受者致敏状态的一个敏感指标,对其动态监测有助于筛选合适供者和预测排斥反应的发生;血浆置换法处理高致敏状态,效果不佳。     

肾移植受者血清群体反应性抗体水平与术后早期排斥反应间的关系

目的 探讨肾移植受者血清群体反应性抗体(PRA)水平与术后早期排斥反应间的关系.方法 对256例肾移植受者术前测定其血清PRA水平,并对PRA与术后早期排斥反应(超急性、加速性、急性排斥反应)之间的关系进行分析.结果 PRA阴性组、轻度致敏组、高致敏组3组间术后早期排斥反应发生率差异有统计学意义(χ2=78.23,P＜0.01),组间两两比较,差异有统计学意义(q=-8.32～-2.87, P＜0.05、0.01).男性组PRA阳性率低于女性组(χ2=14.18,P＜0.01);无输血史组PRA阳性率低于有输血史组(χ2=5.39,P＜0.05);有妊娠史组与无妊娠史组PRA阳性率比较差异无显著性(χ2=0.66,P＞0.05);二次移植组PRA阳性率明显高于初次移植组(χ2=20.10,P＜0.01).结论 输血、再次移植是PRA阳性的危险因素.随着PRA水平的升高,术后早期排斥反应的发生率升高.肾移植受者血清低水平的PRA可降低术后早期排斥反应的发生,提高人、肾生存期.     

血浆置换在肾移植致敏受者中的应用及护理

目的　探讨术前血浆置换(PE)对肾移植致敏受者的治疗效果。　方法　25例血清群体反应抗体(PRA) >10% (10% ~82% )的肾移植受者,术前行PE治疗,观察治疗前后血清免疫球蛋白、PRA的变化,以及肾移植后的排斥反应发生率。　结果　25例PE治疗后血清免疫球蛋白IgG、IgM、IgA均有明显下降(P<0. 01)。有20例经1~3次PE后PRA下降至10%以下,肾移植后发生排斥反应5例,发生率25%; 5例PE治疗后PRA仍大于10%,暂未行肾移植术。　结论　对于高PRA患者,肾移植前PE能有效降低术后排斥反应发生率。熟练操作,专人护理是保证治疗顺利进行的关键。     

肿瘤坏死因子-α、白介素-10基因型多态性在致敏受者肾移植急性排斥反应中的意义

目的　研究致敏受者肿瘤坏死因子 -α(TNF -α)、白介素 -10 (IL -10 )基因型多态性与肾移植术后急性排斥反应的关系。方法　应用序列特异性引物聚合酶链反应 (PCR -SSP)方法对 97例术前群体反应性抗体 (PRA)阳性肾移植受者的TNF -α、IL -10的基因型进行测定 ,探讨其对急性排斥反应发生率的影响。结果　 97例致敏肾移植受者术后 3个月内共有 2 3例次发生了急性排斥反应 ,其中TNF -α高产量基因型组受者和IL -10高产量基因型组受者的急性排斥反应发生率分别高达 5 1 9%和 5 5 5 %,显著高于相应的低产量基因型受者的 12 9%和 13 3 %,差异有显著性 (P均 <0 0 1)。联合TNF -α和IL -10发现 ,高TNF -α产量基因型和高、中IL -10基因型受者的急性排斥反应发生率为 62 5 %,明显高于两者均为低产量基因型者的 8 5 %,差异有显著性 (P <0 0 1)。结论　TNF -α和IL -10基因型多态性对致敏受者肾移植术后的急性排斥反应发生率有明显影响 ,测定TNF -α和IL -10基因型有利于制订合理的免疫抑制方案     

诱导治疗对肾移植急性排斥反应的预防作用

目的观察诱导治疗对肾移植术后急性排斥反应的预防作用。方法45例肾移植患者行术前诱导治疗,其中组反应性抗体(PRA)阴性患者23例,行赛尼哌诱导治疗13例,ALG诱导治疗4例,OKT3诱导治疗6例;PRA阳性患者22例,行赛尼哌诱导治疗11例,ALG诱导治疗5例,OKT3诱导治疗6例。结果45例患者均行肾移植手术。23例PRA阴性患者中,术后3个月内无急性排斥反应发生,一年内急性排斥反应发生率为22%,与同期相同条件患者(26%)比较,差异无统计学意义;22例PRA阳性患者术后无超急排斥反应发生,1例(4.5%)发生加速排斥反应。术后3、6个月内急性排斥反应发生率分别为18.2和27.2%,与同期PRA阳性患者比较,差异无统计学意义;一年内人、肾存活率分别为90.9和81.8%,与术前无诱导治疗的PRA阳性患者(87.0、72.0%)比较,差异有统计学意义(P<0.01)。结论对于PRA阴性患者,诱导治疗预防肾移植术后急性排斥反应的作用不明显,但对PRA阳性患者,诱导治疗能有效预防急性排斥反应的发生,显著提高移植肾的长期存活率。     

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.     

PRA配型技术在肾移植中的应用研究

目的 探讨群体反应性抗体（PRA）配型新技术对肾移植近远期的效果。方法 854例患者肾移植前运用PRA新技术进行组织配型,并行血浆置换,未采用PRA组配型的423例作为对照,观察肾移植术后免疫指标变化、近期（AR）发生率以及对长期存活的影响。结果 未采用PRA组织配型组发生超急性排斥反应（HR）9例（2.1%)、急性排斥反应198例（47%）;1年人/肾存活率86.7%/76.3%、3年人/肾存活率725%/67.9%、5年人/肾存活率69.5%/d49.3%。采用PRA配型新技术共854例,肾移植术后未发生超急性排斥反应,发生急性排斥反应162例（19.0%),1年人肾存活率达97.3%/49.3% 。采用PRA配型新技术共854例,肾移植术后未发生超急性排搞清反应,发生急性排斥反应162例（19.0%),1年人肾存活率达97.3%/95.0%、3年人肾存活率92.0%/84.2%、5年人/肾存活率87.0%/81.6%。结论 PRA阴性配型可杜绝超急性排斥反应发生,降低急性排斥反应发生率,提高人/肾长期存活率。     

Preoperative single-bolus high-dose antithymocyte globulin as induction therapy in sensitized renal transplant recipients

Background Immunological sensitization remains a major problem following renal transplantation. There is no consensus for the management of sensitized renal allograft recipients. The patients become tethered to dialysis while waiting for compatible donors. This study was designed to evaluate the efficacy and safety of preoperative single- bolus high-dose antithymocyte globulin (ATG) as induction therapy in sensitized renal transplant recipients.Methods A total of 56 patients were divided into two groups according to the level of panel reactive antibody (PRA): non-sensitized group (PRA&lt;10%, n=30) and sensitized group (PRA≥10%, n=26). The characteristics of the recipients and donors were comparable between the two groups. Mycophenolate mofetil (MMF, 1 g) or ATG (iv. 9 mg/kg) were given preoperatively in the two groups as induction therapy. After the transplantation, the patients were treated with standard triple therapy regimen consisting of tacrolimus (FK-506) or cyclosporine A, MMF, and prednisolone. Acute rejection (AR) and infection episodes were recorded and renal function was monitored during a 12-month follow-up. χ(2) test and t test were used to analyze the data.Results During the follow-up, 6 patients (20.0%) suffered AR episodes in the non-sensitized group and 4 (15.4%) in the sensitized group (P=0.737); 8 patients (26.7%) experienced 11 infection episodes (average, 1.4 episodes per infected patient) in the non-sensitized group, and 6 (23.1%) experienced 10 infection episodes (average, 1.7 episodes per infected patient) in the sensitized group (P=0.757, 0.890). The safety of the drugs, which was assessed by the occurrence of side effects, was comparable between the two groups. The hospital stay was 13－25 days (mean, 16.7±3.3) in the non-sensitized group and 14－29 days (mean, 16.2±3.1) in the sensitized group, respectively (P=0.563). No delayed graft function (DGF) was observed in all the patients. Both the 12-month actuarial patient and graft survival rates were 100% in the two groups.Conclusion Preoperative single-bolus high-dose ATG is an effective and safe induction therapy yielding acceptable acute rejection rate in sensitized renal transplant recipients.     

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.

     

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…     

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.     

肾移植致敏受者的配型研究及应用

目的:探讨人类白细胞抗原(HLA)配型在肾移植致敏受者中的应用及意义。方法:对32例PRA阳性的肾移植受者采用HLA交叉反应组(CREGs)配型原则选择供者,观察其供受者相配情况及移植效果。结果:按交叉反应组配型原则,供受者HLACREGS+DR0,1,2和3错配(MM)分别为8例(25％)、10例(31.25％)、12例(37.5％)和2例(6.25％),无4～6错配;而按传统的HLA-A,B,DR抗原配型原则,其0,1,2,3和4MM分别为2例(6.25％)、3例(9.38％)、10例(31.25％)、9例(28.12％)和8例(25％),其中0～1错配仅有5例。肾移植术后仅有9例发生急性排斥反应,经OKT_3治疗逆转,所有受者术后肾功能均恢复正常。结论:良好的HLA CREGs配型,可以显著提高供受者相配率,对减少致敏受者的排斥反应,提高移植肾存活率具有重要的意义。     

肾移植患者围手术期群体反应性抗体检测的临床意义

目的:研究肾移植患者围手术期群体反应性抗体(PRA)的水平与移植肾急性排斥的关系。方法:采用ELISA-PRA检测法,对34例尸体肾移植患者进行手术前、术后1周、术后2周、术后1个月血清PRA检测,并分析其结果与肾移植急性排斥的关系。结果:34例患者中,移植前PRA阳性者(PRA)>10％)9例(26.5％),有5例PRA>50％(51％～80％),术前行血浆置换。PRA阴性者25例(73.5％)。PRA阳性组中,有5例发生急性排异,其中2例切除移植肾恢复血液透析。PRA阴性组中,有4例发生急性排异,治疗后肾功能恢复正常。两组相比排异发生率有统计学差异(P<0.05)。术后PRA阳性者11例(术前PRA阴性转阳者2例),发生排异6例(1例为术前PRA阴性)。术后PRA阴性者中,有3例发生排异。两组相比排异发生率有统计学差异(P<0.05)。结论:①患者肾移植术前体内PRA水平对移植肾排异有显著影响;②患者肾移植术后体内PRA水平影响移植肾急性排异的发生和转归。     

肾移植群体反应性抗体检测641例分析

目的探讨群体反应性抗体检测(PRA)对于肾移植的意义。方法采用ELISA方法对641例肾移植患者进行PRA检测:术前570例、术后71例。结果570例术前检测PRA,阴性490例,术后发生急性排斥反应35例;弱阳性68例,术后发生急性排斥反应36例;12例阳性术后检测仍为阳性,发生急性排斥反应10例。71例术后检测PRA,阴性59例,发生急性排斥反应3例;阳性12例,发生急性排斥反应7例。结论肾移植患者术前检测PRA有助于减少排斥反应的发生。     

免疫吸附在高致敏肾移植受者中的应用

目的 探讨蛋白A免疫吸附(IA)治疗在预防高致敏肾移植受者急性排斥反应中的效果和安全性.方法 回顾性分析2008年3月至2009年10月首都医科大学附属北京朝阳医院收治的12例群体反应性抗体(PRA)高的肾移植患者在术前应用IA治疗的临床资料.比较治疗前后血免疫球蛋白IgG、IgM、IgA及PRA水平.观察患者术后急性排斥反应发生情况及不良反应.结果 12例患者IA治疗次数为3～8次.治疗后PRA Ⅰ和Ⅱ类抗体均较治疗前明显下降[14%(4%,27%)比86%(73%,98%),6%(0,23%)比68%(34%,88%),均P＜0.01];血清总IgG水平较治疗前明显下降[(550±341)g/L比(1301±393)g/L,P＜0.01];IgA和IgM也较治疗前降低[(144±78)g/L比(185±93)g/L,(103±48)g/L比(131±66)g/L,P＜0.01].5例患者在术后发生了急性排斥反应,给予抗胸腺细胞球蛋白(ATG)或联合IA(2例)治疗后均逆转.术后6个月内,1例患者发生烟曲霉菌肺炎,2例出现卡氏肺囊虫肺炎,均治愈.结论 IA治疗可降低高致敏患者体内预存抗体水平.辅以诱导治疗对预防和减轻肾移植术后排斥反应疗效确切.