可溶性CD20在肾移植排斥反应中的表达及其意义

目的 观察血清中可溶性CD20分子(sCD20)在肾移植急性排斥反应时的变化,探讨血清sCD20水平变化与移植肾预后的关系.方法 收集50例肾移植患者外周血,酶联免疫吸附测定法检测血清中sCD20水平.结果 25例急性排斥反应患者术前血清sCD20为(1750.60±359.59) ng/L,与稳定组(936.96±181.71) ng/L比较,差异有统计学意义(P＜0.05);移植术后急性排斥反应组血清sCD20为(2516.20 ±511.33) ng/L,与稳定组(988.40 ±215.78)ng/L比较,差异有统计学意义(P＜0.05);而且sCD20值水平较高的患者移植肾存活时间明显少于sCD20值水平较低的患者.结论 CD20分子在移植肾急性排斥反应和预测肾移植预后中可能起重要作用.     

抑制性受体CD305表达在移植肾排斥反应监测中的意义

目的 探讨抑制性受体CD205的表达在移植肾排斥反应中的意义.方法 应用双单克隆抗体夹心ELISA法检测153例肾移植术后患者血清中可,溶型CD305(sCD305)的表达水平,20例健康志愿者标本作为对照组.结果 对照组和98例移植肾功能正常患者血清sCD305表达分别为(4.3±2.3)和(6.3±3.7)μg/L.20例移植肾急性排斥及5例移植肾失功患者血清sCD205表达明显增加,分别为(36.3±14.7)和(28.8土9.4)μg/L,显著高于对照组和移植物功能正常组(P＜0.01).30例移植.肾慢性排斥及6例尿毒症透析患者血清sCD205分别为(13.1±5.5)和(11.2±4.6)μg/L,亦明显高于对照组和移植肾功能正常组(P=0.00).结论 发生移植肾排斥反应的患者血清sCD3205有较高水平的表达,可望作为移植肾排斥反应的监测指标之一.     

排斥反应时血清可溶性白细胞相关免疫球蛋白样受体1的水平及意义

目的 探讨可溶性白细胞相关免疫球蛋白样受体1(sLAIR-1)与移植物排斥反应的相关性.方法 采用双抗体夹心酶联免疫吸附试验测定23例肝移植、139例肾移植患者的血清sLAIR-1水平,并以健康志愿者为对照.结果 健康志愿者的血清sLAIR-1水平为(4.3±2.3)μg/L,移植器官功能正常者(肝移植11例,肾移植87例)的sLAIR-1为(6.3±3.7)μg/L,二者比较,差异无统计学意义(P>0.05).肝移植后发生急性排斥反应的6例患者,其血清sLAIR-1水平为(47.2±25.9)μg/L;肾移植后后发生急性排斥反应的20例患者,其血清sLAIR-1水平(36.3±14.7)μg/L;移植肾功能丧失的5例患者,其血清sLAIR-1水平为(28.8±9.4)μg/L,上述三者的血清sLAIR-1水平均明显高于移植物功能正常者和健康志愿者(P<0.01).移植肝重度排斥反应的1例,其血清sLAIR-1高达117.3μg/L,为正常人的27倍.移植肝慢性排斥反应者(5例)和移植肾慢性排斥反应者(27例)的血清sLAIR-1水平分别为(16.1±6.4)μg/L和(13.1±5.5)μg/L,也明显高于移植物功能正常者和健康志愿者(P<0.05).结论 发生排斥反应者的血清sLAIR-1水平升高,其水平的升高可能是发生排斥反应的重要风险因素.     

可溶型LAIR分子与肾移植术后巨细胞病毒肺炎的关系

目的 探讨可溶型LAIR分子(sCD305,CD306)与肾移植术后巨细胞病毒(CMV)肺炎的关系. 方法肾移植受者血清19份,分为肺炎组(10份)和对照组(9份);以夹心ELISA方法定量检测血清中sCD305和CD306的浓度;用CHISS软件进行:检验. 结果 2组sCD305浓度均不符合正态分布,肺炎组波动于0.000～3.039 μg/L,对照组波动于0.000～8.375μg/L;肺炎组CD306浓度不符合正态分布,波动于0.000～0.017 μg/L,对照组符合正态分布.浓度为(0.046±0.035)μg/L;CD306在CMV肺炎患者血清内的表达降低,与对照组相比差异有统计学意义(P=0.000),而sCD305在2组的表达差异无统计学意义(P=0.316). 结论 CD306在肾移植术后发生CMV肺炎的患者血清内表达明显降低,CMV-PP65抗原检测联合CD306检测,有助于临床准确早期诊断CMV肺炎.     

CD44分子在肾移植患者急性排斥反应肾组织中的表达及意义

目的:探讨CD44分子与肾移植急性排斥反应的关系。方法:回顾分析2005年7月～2009年5月间肾移植术后穿刺病理活检证实为急性排斥反应患者28例的CD44在移植肾组织中的表达。结果:28例急性排斥反应肾组织中有25例CD44呈阳性表达,阳性率为89.29%;10例慢性排斥反应肾组织中有3例阳性表达,阳性率为30%;30例正常肾脏组织中5例CD44分子的阳性表达,阳性率为16.7%;两两比较,结果差异有统计学意义(P0.05)。结论:CD44与其与配体的相互作用在移植肾急性排斥反应中可能起到重要作用,CD44分子有可能成为一个特异性和敏感性都较好的早期诊断急性排斥的预测因子。     

CD44在大鼠肾移植急性排斥反应中的表达

目的:探讨移植肾组织CD44的表达及血清中可溶性CD44的含量与急性排斥反应的关系。方法:雄性Wistar大鼠和SD大鼠分别作为供体和受体,共分为四组,采用改进的Blom法大鼠原位肾移植模型。免疫组织化学染色法检测移植肾组织CD44分子的表达;酶联免疫吸附试验测定术后血清中可溶性CD44水平的变化。结果:移植肾组织CD44分子的表达在同种异体移植组显著高于同品系移植组、手术对照组及药物治疗组(均P<0.05);移植肾组织CD44分子的表达与急性排斥反应呈正相关(皮质:r=0.734,髓质:r=0.670,均P<0.01);发生急性排斥反应的移植肾组织CD44分子的表达与Banff急性排斥反应指数无相关性(P>0.05);血清中可溶性CD44分子各组间差异无统计学意义,与急性排斥反应及Banff指数均无相关性(均P>0.05)。结论:CD44分子在肾移植急性排斥反应的发病机制中起着重要作用,为进一步提高移植排斥反应防治水平提供理论依据。     

细胞免疫能量测定在肾移植中的应用

目的 探讨适用于评价肾移植受者免疫状态的新方法.防止移植后的排斥反应和感染,提高人/肾生存质量和存活率.方法 应用ImmuKnow~(TM)-Cylex检测技术测定肾移植受者细胞免疫能量(三磷酸腺苷,ATP).收集62例肾移植受者术前(术前组)、术后稳定期(术后稳定组)、发生感染(术后感染组)和排斥反应(排斥反应组)等不同时期的肝素钠抗凝样本共150份.通过测量CD4+T淋巴细胞受刺激后释放的ATP浓度来判定细胞免疫力.并用秩和检验和两两比较统计方法,对结果进行分析和比较.结果 各组肾移植受者CD4+T淋巴细胞ATP浓度分别为:术前组(281.33±146.46)/μg/L、术后稳定组(310.19±147.12)/μg/L、术后感染组(142.41±118.26)μg/L、排斥反应组(332.77±154.44)μg/L;术后感染组ATP浓度显著低于其他各组.差异均有统计学意义(P<0.05).结论 LmmuKnow~(TM)-Cylex细胞免疫能量测定具有灵敏度高、特异性强、简便易操作等优点,适合于肾移植受者免疫状态的临床监测,特别是对术后感染有很好的预警作用,对指导感染后免疫抑制剂的个体化用药具有一定的参考价值.     

肾移植排斥反应时血浆骨桥蛋白水平的变化及意义

目的 探讨肾移植排斥反应时血浆骨桥蛋白( OPN)水平的变化及意义.方法 对46例肾移植受者的临床资料及生物样本进行回顾性分析.根据移植肾组织学检查结果,46例受者被分为3组:移植肾功能稳定,且移植肾组织学检查未显示有排斥反应证据者16例,为非排斥组;移植肾组织学检查证实有急性细胞性排斥反应者22例,为急排组;移植肾组织学检查证实为慢性移植肾肾病(CAN)者8例,为慢排组.另以6名亲属活体供者作为对照组.于移植肾组织样本采集前抽取外周血,用人OPN酶联免疫吸附试验检测试剂盒测定血浆OPN水平,参照Banff 03标准对排斥反应进行分级.结果 对照组血浆OPN水平为(12.23±5.95)μg/L,非排斥组稍高,为(19.38±8.23)μg/L,两组间的差异无统计学意义( P＞0.05);慢排组血浆OPN水平为(27.77±12.27)μg/L,与非排斥组比较,差异无统计学意义(P＞0.05);急排组血浆OPN水平为(41.84±18.51)μg/L,与非排斥组比较,差异有统计学意义(P＜0.05),与慢排组比较,差异也有统计学意义(P＜0.05).急排组血浆OPN水平与排斥反应的级别具有正相关性(r=0.87,P＜0.05),发生Ⅰa级排斥反应和Ⅱb级排斥反应者间血浆OPN水平的差异有统计学意义(P＜0.05).结论 血浆OPN水平变化与急性排斥反应关系密切,其水平高低与排斥反应的级别呈正相关,可以作为诊断移植肾急性细胞性排斥反应、评估其严重程度的一个辅助指标.     

血清中可溶性CD44v6含量和组织中CD44v6蛋白表达研究

目的　研究胃癌患者外周血中sCD44v6含量及其组织中CD44v6蛋白表达 ,探讨sCD44v6含量 /CD44v6蛋白与临床病理参数之间的关系。方法　应用酶联免疫吸附试验 (ELISA)检测胃癌患者 (术前 )及其中部分术后及健康对照组血清中sCD44v6含量并以 (S P)免疫组织化学法测定相应组织中CD44v6蛋白的表达。结果　 70例胃癌患者血清中sCD44v6含量 (2 .15± 0 .78)μg/L明显高于 16例正常对照组 (1.18± 0 .43 ) μg/L、14例根治性手术后血清中sCD44v6含量(1.2 1± 0 .3 9) μg/L比术前 (2 .67± 0 .83 ) μg/L明显下降 (P <0 .0 1) ,而 6例非根治性手术后(3 .2 9± 0 .41) μg/L比术前 (3 .61± 0 .49) μg/L下降不明显 (P >0 .0 5 )。结论　胃癌患者外周血中sCD44v6含量及组织中CD44v6蛋白表达的变化与转移、临床分期、病理分期有关 ,sCD44v6含量升高可作为胃癌患者淋巴结转移 (尤其是早期转移 )的监测指标。     

肾移植术后早期血清可溶性CD14水平的检测及意义

目的了解肾移植术后早期血清可溶性CD14(sCD14)水平变化规律及意义。方法连续选取51例肾移植患者,检测术前1h和术后1～10d血清sCD14水平,观察肾功能恢复情况。根据术后2周内发生排斥反应与否分为排斥组和无排斥组,将2组患者的血清sCD14水平和血肌酐(Scr)水平进行比较。结果51例中发生排斥反应13例,发生排斥反应平均时间为7d。术前1h排斥组和无排斥组Scr分别为(789±221)和(742±234)μmol/L,2组比较差异无统计学意义。术后1～10d Scr水平排斥组高于无排斥组,其中第3、5～10天2组Scr水平差异有统计学意义(P＜0.05),分别为(237±104)和(160±70)、(176±85)和(117±46)、(174±81)和(112±40)、(173±81)和(112±39)、(209±53)和(112±38)、(203±73)和(103±35)、(181±50)和(102±31)μmol/L。术前1h血清sCD14排斥组为(9.55±5.71)mg/L,与无排斥组(8.99±3.89)mg/L相比差异无统计学意义。术后第1～5天血清sCD14水平排斥组均高于无排斥组,分别为(15.52±6.60)和(9.85±4.11)、(15.48±5.85)和(7.53±3.79)、(12.15±4.45)和(5.88±3.95)、(10.84±4.11)和(4.88±3.17)、(7.61±5.37)和(4.66±1.91)mg/L,差异有统计学意义(P＜0.05)；排斥组和无排斥组术后第1天血清sCD14水平均较术前明显升高,而后呈逐渐下降趋势。结论肾移植术后sCD14水平升高早于临床急性排斥反应,术后前5d内的sCD14水平可作为预测急性排斥反应的重要依据。     

Renal expression of CD44 correlates with acute renal allograft rejection

As CD44 is involved in the activation, proliferation, adhesion, and extravasation of lymphocytes, we hypothesized that CD44 could be involved in the pathogenesis of acute renal allograft rejection. Renal biopsies and plasma were collected from patients suffering an episode of acute renal allograft rejection. CD44 and its ligands, hyaluronic acid (HA) and osteopontin, were analyzed retrospectively by immunohistochemistry and, computer-aided, morphometric analysis. Soluble CD44 (sCD44) and osteopontin in the plasma were determined by enzyme-linked immunosorbent assay. During acute rejection episodes, CD44 and its ligands, HA and osteopontin, were upregulated in the renal allograft. Also, increased sCD44 plasma levels were observed, which correlated with both tubular expression of CD44 and the extent of infiltrate. No differences could be detected between the different pathologic grades of rejection. Upregulation of tubular CD44 and increased levels of circulating sCD44 may reflect a common pathogenic mechanism during acute renal rejection and could be useful markers in the diagnosis of acute renal rejection.     

肾移植患者急性排斥反应与sCD30的相关性

目的 研究检测肾移植患者手术前后血清溶解性CD30（sCD30）水平的临床意义。方法 采用酶联免疫吸附剂测定法（ELISA）检测69例肾移植患者术前及术后sCD30的水平，并分析sCD30与肾移植受者术后急性排斥发生的关系。结果 术前sCD30阳性患者11例，其中有6例发生急性排斥，sCD30阴性患者58例，发生急性排斥5例。两组相比排斥反应发生率差异有统计学意义（P〈0．01）。术后5dsCD30在发生排斥患者组中的水平与对照组间差异有统计学意义（P〈0．05），而术后1、3d水平两组间差异无统计学意义（P〉0．05）。结论 肾移植手术前后监测sCD30水平，特别是术前及术后第5天左右时的检测水平，对于评估和预测急性排斥反应发生的可能性，具有重要的参考价值。     

Plasma levels of soluble CD30 in kidney graft recipients as predictors of acute allograft rejection

In renal transplant recipients elevated soluble serum CD30 levels are associated with increased rejection and graft loss. We sought to determine the sCD30 plasma levels before and after kidney transplantation and to assess whether sCD30 was a predictive factor of immunological risk. sCD30 plasma levels were determined by an enzyme-linked immunosorbent assay assay in 52 kidney graft recipients before as well as 7, 15, and 21 days after transplantation. Eighteen patients developed acute allograft rejection (group I) and 34 patients showed uneventful courses (group II). Before transplantation sCD30 plasma levels were elevated in both groups (mean: 162.6 +/- 89.5 U/mL). After transplantation, group I recipients with acute rejection showed higher relative levels of plasma sCD30 on days 7 and 15 (120.8 +/- 74.6 U/mL and 210.6 +/- 108.7 U/mL respectively) compared with group II patients without rejection (95 +/- 45 U/mL and 59.4 +/- 31.6 U/mL), a difference that was significant for group I (P = .0003) and not significant for group II (P = .09). On day 21, sCD30 decreased in the two groups but remained higher among group I patients (120.6 +/- 92.7 U/mL). HLA antibodies were positive in 18 patients (34.6%) with 9 (50%) experiencing at last one episode of acute rejection. Among 34 patients negative for anti-HLA antibodies, nine displayed acute rejection only (26.4%), a difference that was not significant (P > .05). If we consider 100 U/mL as the minimum predictive level for allograft rejection, our results suggested that levels of sCD30 should be taken into consideration with the presence of HLA-antibodies detectable before and after transplantation, especially in patients with more than three HLA mismatches [RR = 3.20 (0.94 < RR < 10.91)]. These data suggested that measurement of plasma sCD30 is a useful procedure for the recognition of rejection in its earliest stages.     

Serial Soluble CD30 Measurements as a Predictor of Kidney Graft Outcome

Background

High levels of soluble CD30 (sCD30), a marker for T-helper 2-type cytokine-producing T cells, pre or post-renal transplantation serves as a useful predictor of acute rejection episodes. Over the course of 1-year, we evaluated the accuracy of serial sCD30 tests to predict acute rejection episodes versus other pathologies that affect graft outcomes.

Patients and methods

Fifty renal transplant recipients were randomly selected to examine sCD30 on days 0, 3, 5, 7, 14, and 21 followed by 1, 3, 6, and 12 months. The results were analyzed for development of an acute rejection episode, acute tubular necrosis (ATN), or other pathology as well as the graft outcome at 1 year.

Results

Compared with pretransplantation sCD30, there was a significant reduction in the average sCD30 immediately posttransplantation from day 3 onward (P < .0001). Patients were divided into four groups: (1) uncomplicated courses (56%); (2) acute rejection episodes (18%); (3) ATN (16%); and (4) other diagnoses (10%). There was a significant reduction in sCD30 immediately posttransplantation for groups 1, 2, and 3 (P < .0001, .004, and .002 respectively) unlike group 4 (P = .387). Patients who developed an acute rejection episode after 1 month showed higher pretransplantation sCD30 values than these who displayed rejection before 1 month (P = .019). All groups experienced significant improvement in graft function over 1-year follow-up without any significant differences.

Conclusion

Though a significant drop of sCD30 posttransplantation was recorded, serial measurements of sCD30 did not show a difference among subjects who displayed acute rejection episodes, ATN, or other diagnoses.     

Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury

Mesenchymal stem cells (MSC) were recently shown to migrate to injured tissues when transplanted systemically. The mechanisms underlying the migration and homing of these cells is, however, unclear. In this study, we examine the role of CD44 and its major ligand, hyaluronic acid, in the trafficking of intravenously injected MSC in the glycerol-induced mouse model of acute renal failure (ARF). In vitro, hyaluronic acid promoted a dose-dependent migration of the stem cells that was inhibited by an anti-CD44 blocking monoclonal antibody. In vivo, stem cells injected into mice with ARF migrated to the injured kidney where hyaluronic acid expression was increased. Their presence correlated with morphological and functional recovery. Renal localization of the MSC was blocked by pre-incubation with the CD44 blocking antibody or by soluble hyaluronic acid. Stem cells derived from CD44 knockout mice did not localize to the injured kidney and did not accelerate morphological or functional recovery. Reconstitution by transfection of CD44 knockout stem cells with cDNA encoding wild-type CD44, but not a loss of function CD44 unable to bind hyaluronic acid, restored in vitro migration and in vivo localization of the cells to injured kidneys. We suggest that CD44 and hyaluronic acid interactions recruit exogenous MSC to injured renal tissue and enhance renal regeneration.     

Immunological monitoring after organ transplantation: potential role of soluble CD30 blood level measurement

Analysing the relevance of soluble CD30 (sCD30) in the bloodstream before and after transplantation may be important for the monitoring of transplant recipients. In this study, 27 patients (15 pediatric liver and 12 adult kidney graft recipients) were investigated. In the liver graft group, the patients who developed acute rejection during the first month (n=9) had a slightly higher sCD30 value on pre-transplantation baseline (day 0) and post-transplantation day 7, when compared to patients with normal graft function (n=6) (day 0: 102(1.6) U/ml versus 118(1.5) U/ml, p=0.52) and (day 7: 69(1.5) U/ml versus 83(1.6) U/ml, p=0.47). Increased serum sCD30 was shown to correlate with increased interleukin-10 circulating levels between day 0 and day 7 (r=0.53; p=0.04), whereas, no correlation could be evidenced between interferon-gamma (IFN-gamma) and sCD30 (r=0.02; p=0.47). Similarly, in the kidney transplantation group, no significant difference was found in sCD30 levels at day 0 in both groups with graft rejection or normal graft function (n=6) (85(1.3) U/ml versus 77(1.6) U/ml, p=0.66), but sCD30 decreased significantly at day 7 post-transplantation from baseline value in the rejection group (n=6) (77(1.6) versus 35(1.4); p=0.02). We conclude that increased serum sCD30 was correlated with increased IL-10 (interleukin-10) circulating levels, but not with IFN-gamma levels in the post-transplantation period. Neither pre-transplantation sCD30 nor sCD30 at day 7 post-transplantation could be correlated with acute rejection in liver graft recipient. The monitoring of sCD30 might constitute a tool to assess the risk of acute rejection in renal transplant but did not appear as a valuable mean for early immunological monitoring in the small group of liver allograft recipients patients analysed in this study.     

Soluble CD30 and Cd27 levels in patients undergoing HLA antibody-incompatible renal transplantation

HLA antibody-incompatible transplantation has a higher risk of rejection when compared to standard renal transplantation. Soluble CD30 (sCD30) has been shown in many, but not all, studies to be a biomarker for risk of rejection in standard renal transplant recipients. We sought to define the value of sCD30 and soluble CD27 (sCD27) in patients receiving HLA antibody-incompatible transplants. Serum taken at different time points from 32 HLA antibody-incompatible transplant recipients was retrospectively assessed for sCD30 and sCD27 levels by enzyme-linked immunosorbent assay (ELISA). This was compared to episodes of acute rejection, post-transplant donor-specific antibody (DSA) levels and 12 month serum creatinine levels. No association was found between sCD27 and sCD30 levels and risk of acute rejection or DSA levels. Higher sCD30 levels at 4–6 weeks post-transplantation were associated with a higher serum creatinine at 12 months.Conclusion patients undergoing HLA antibody-incompatible transplantation are at a high risk of rejection but neither sCD30 (unlike in standard transplantation) nor sCD27 was found to be a risk factor. High sCD30 levels measured at 4–6 weeks post-transplantation was associated with poorer graft function at one year.