肝移植后受者淋巴细胞亚群表达与免疫平衡

背景:有文献报道,肝移植后受者外周血淋巴细胞的变化较肝脏酶学的改变更为敏感,其特异性有待进一步研究。目的:分析淋巴细胞亚群中CD3-/HLA-DR+,CD3+/CD25+和CD3+/HLA-DR-与肝移植受者机体免疫状况和并发症的关系。方法:应用全自动生化分析仪和流式细胞分析仪检测56例肝移植受者移植后肝功能和淋巴细胞亚群,依照肝功能情况划分为肝功能正常组52例和肝功能异常组27例,肝功能异常组中分为急性排斥组7例、药物反应组11例和原因不明组9例。分析各组肝移植受者CD3-/HLA-DR+,CD3+/CD25+和CD3+/HLA-DR-表达水平与其并发症的关系。结果与结论:肝功能正常组CD3-/HLA-DR+和CD3+/CD25+的表达水平低于肝功能异常组(P=0.011,0.002),CD3+/HLA-DR-的表达高于肝功能异常组(P=0.012)。CD3-/HLA-DR+和CD3+/CD25+在急性排斥组的表达水平明显高于药物反应组(P=0.039,0.048),急性排斥组CD3+/HLA-DR-的表达水平低于药物反应组(P=0.007)。提示CD3-/HLA-DR+,CD3+/CD25+和CD3+/HLA-DR-的表达水平与肝移植后受者机体免疫状况及并发症密切相关,可作为判断肝移植后受者并发症的辅助指标以及进行免疫干预的参考依据。     

肾移植后急性体液排斥反应：5年同一机构296例随访*

背景：肾移植后急性体液排斥反应虽然发生率不高,但对移植物功能恢复可造成严重影响,是移植物早期丢失的主要原因。 目的：分析肾移植后急性体液排斥反应早期诊断和防治的意义。 方法：选择接受肾移植后规律随访的受者296例,其中移植前群体反应性抗体阳性受者26例,阴性受者270例。酶联免疫吸附试验动态监测肾移植受后外周血中的群体反应性抗体和供者特异性抗体,免疫组织化学染色观察穿刺活检组织中C4d的沉积及浸润淋巴细胞表面分子标记,按Banff 2005标准结合临床相关指标诊断急性体液排斥反应。 结果与结论：26例移植前群体反应性抗体阳性受者中6例(23%)移植后发生了急性体液排斥反应,270例阴性受者中19例(7%)发生了急性体液排斥反应,差异有显著性意义(P < 0.01)。发生急性体液排斥反应的患者中22例(88%)外周血清中检测到供者特异性抗体,271例无急性体液排斥反应的患者中仅1例检出供者特异性抗体,差异具有显著性意义(P < 0.01)。急性体液排斥反应受者中C4d阳性率为80%,未发生急性体液排斥反应的患者C4d阳性率仅为6.7%,差异具有显著性意义(P < 0.001)。肾移植后早期监测群体反应性抗体和供者特异性抗体水平,通过穿刺活检观察移植肾组织中的C4d沉积情况,可及时诊断急性体液排斥反应,有效改善移植物功能并提高移植物存活率。关键词：肾移植;供者特异性抗体;急性体液排斥反应;C4d;利妥昔单抗  doi:10.3969/j.issn.1673-8225.2012.18.005 中图分类号: R617  文献标识码: A   文章编号: 1673-8225(2012)18-03249-06     

流式细胞技术检测肾移植后外周血白细胞介素18受体的表达

背景：细胞因子常常在肾移植后排斥反应早期即被释放,因此可以作为排斥反应的早期诊断指标。 目的：观察尿毒症患者肾移植前后外周血白细胞介素18受体(IL-18R)表达的变化。 方法：将2004-09/2005-09在解放军济南军区总医院进行的肾移植尿毒症32例患者分为肾功能稳定组24例,急性排斥组8例。另选择以往手术后移植肾功能正常,平均存活时间4年的肾移植患者12例为长期存活组。同期查体未发现异常健康自愿者7例为健康对照组。提取受试者的外周血淋巴细胞,加入双荧光标记的鼠抗人CD4/IL-18Rα及CD8/IL-18Rα单克隆抗体,利用流式细胞仪进行测定。 结果与结论：流式细胞技术检测CD4/IL-18Rα及CD8/IL-18Rα在尿毒症组的阳性率明显高于健康对照组(P=0.02,P=0.04)。肾功能稳定组及长期存活组外周血CD4/IL-18Rα及CD8/IL-18Rα的表达明显低于急性排斥组(P < 0.05)。急性排斥反应组激素冲击治疗后其阳性率明显低于激素冲击治疗前(P < 0.05)。3例耐激素排斥反应者IL-18R表达值高于5例激素治疗有效者。结果显示外周血CD4/IL-18Rα及CD8/IL-18Rα的变化可以较早预测肾移植后急性排斥反应,预测肾移植后恢复情况,评估排斥反应对激素治疗的效果。     

移植肾急性排斥与移植前后血清细胞因子表达的变化

背景：目前异体器官移植后细胞因子变化己经有较多的报道,但有关细胞因子在肾移植患者中的动态变化规律及其与移植急性排斥反应的关系鲜有报道。 目的：观察肾移植受者移植前后血清细胞因子表达变化,并探讨其与移植肾急性排斥的关系。 方法：选择2008年9月至2011年9月武警后勤学院附属医院收治的接受肾移植患者48例,均为首次肾移植,分为肾功能稳定组和急性排斥反应组。另选择健康体检者30人为对照组。 结果与结论：肾功能稳定组、急性排斥反应组移植前1 d血清肿瘤坏死因子α、白细胞介素6、白细胞介素8水平与对照组相比差异无显著性意义(P > 0.05)。肾功能稳定组血清3种细胞因子水平均于移植后第1天即开始逐渐升高,在3 d时显著升高(P < 0.05),5 d时开始下降,7 d下降显著(P < 0.05),14 d左右趋于降至移植前水平,21-28 d表达稳定在移植前水平。急性排斥反应组血清3种细胞因子水平于移植后第1天即显著升高(P < 0.05),7-14 d维持在高水平 (P < 0.05),21-28 d稳定下降,但仍明显高于移植前(P < 0.05)。相同时间段,急性排斥反应组血清3种细胞因子水平均明显高于肾功能稳定组(P < 0.05)。提示移植后血清肿瘤坏死因子α、白细胞介素6、白细胞介素8动态水平变化在一定程度上反映肾移植受者的免疫反应状态,可作为辅助早期诊断急性排斥反应的免疫生物学指标。     

心脏移植后PBMC表面蛋白分子的表达与组织病理学改变的比较

目的:比较心脏移植前后,外周血单个核细胞(PB-MC)表面蛋白分子的表达与组织病理学改变时相间的差别,探讨免疫分子的活性变化与移植器官排斥反应时间进程间的关系。方法:6例心脏移植患者于术前、术后不同时间点取外周血,用不同荧光单克隆抗体(mAb)标记PBMC表面的蛋白分子后,用流式细胞仪检测MHC-II、CD3、CD4、CD8、HLA-DR和ICAM-I的表达。常规移植术后供心组织病理检查,根据国际器官移植排斥反应的病理诊断标准分级。结果:(1)6例实施心脏移植的患者中,有3例在不同时间发生不同程度的急性排斥反应。(2)发生排斥反应的病例在整个30d的观测期内,CD3、CD4及CD8的表达水平,均高于未发生排斥反应的病例。(3)发生移植排斥反应的患者,其PBMC上HLA-DR的表达于移植术后72h出现高峰,出现高峰的时间较用活组织检查诊断排斥反应的时间早4~7d。(4)发生排斥反应的患者PBMC上MHC-II及ICAM-I的表达,分别于术后3d及2d出现高于术前的表达峰,于术后15d达峰值,峰值的出现时间与病理改变基本同步。结论:(1)心脏移植患者术前的免疫功能状况,与移植术后排斥反应的发生率及严重性有一定的相关性。(2)监测PBMC表面HLA-DR、MHC-II及ICAM-I分子的表达,对临床早期发现心脏移植排斥反应具有一定的指导意义。     

尿CD54+淋巴细胞在肾移植急性排斥反应中的变化

背景：正常肾脏、肾小管上皮和血管内皮细胞仅有少量CD54表达,当发生急性排斥反应时,肾小管上皮细胞和血管内皮细胞CD54表达明显增加,同时大量白细胞浸润;间质浸润细胞和肾小管上皮细胞CD54表达增加。 目的：探讨流式细胞仪检测尿CD54⁺淋巴细胞对移植肾急性排斥反应的诊断价值。 方法：来自解放军成都军区总医院的肾移植后恢复正常者(n=18)、出现急性排斥反应者(n=8)、移植肾功不全者(n=9)以及健康志愿者(n=10)。流式细胞仪比较各组移植前后尿液中CD54⁺淋巴细胞比率变化。 结果与结论：尿CD54⁺淋巴细胞在肾移植患者出现排斥反应时明显增加(P < 0.01),抗排斥治疗后逐渐下降。移植肾功能正常者和移植肾功不全者CD54轻度升高。提示尿液中CD54⁺淋巴细胞水平能准确反映肾移植物移植后患者的免疫状态,可作为肾移植后急性排斥反应的特异标志。     

肾移植后急性排异反应12例

背景：同种异体肾移植后发生的急性排斥反应是移植肾功能减退和最终移植肾丧失的最主要原因之一。有效预防和早期发现与治疗急性排异反应是关系到肾脏移植患者能否长期存活的重要问题。 目的：总结肾移植后1个月内急性排异反应患者治疗过程中免疫抑制剂的应用体会。 方法：选择首次肾移植患者12例,移植后采用霉酚酸酯+环孢素A+甲泼尼龙三联预防排异反应。当肾移植后3~30 d内出现尿量减少、移植肾区胀痛不适、血肌酐升高、尿蛋白增加等不同临床表现,确诊为肾移植后急性排斥反应时,先选用甲强龙500 mg/d静脉滴注,连续3 d。然后改甲泼尼龙24 mg口服1次/d,每5~7 d递减4 mg,至8 mg/d维持。 结果与结论：12例患者成功逆转,其中6例甲强龙冲击疗法成功;不能逆转者选用抗胸腺细胞球蛋白或CD3治疗。4例经抗胸腺细胞球蛋白治疗患者中1例8h内尿量迅速增加,2例24 h内尿量迅速增加,1例72 h后尿量迅速增加;1例选用CD3治疗48 h内尿量迅速增加;1例将环孢素转换为他克莫司治疗,同时服用霉酚酸酯胶囊和甲泼尼龙片。经以上治疗12例患者肾功能逐渐恢复。提示肾移植后早期发现、早期诊断、及时治疗是急性排异反应成功逆转的关键。     

肾移植排斥反应中细胞毒性T淋巴细胞相关抗原4的作用

背景：细胞毒性T淋巴细胞相关抗原4是新近发现的共刺激分子,在肿瘤及自身免疫性疾病中研究较多,在肾移植领域缺少研究。目的：探讨细胞毒性T淋巴细胞相关抗原4在肾移植排斥反应中的作用。方法：纳入肾移植患者50例,根据移植后肾功能分为2组,急性排斥组20例,移植肾功能稳定组30例。同时选择30例健康查体者作为健康对照组。分别抽取外周静脉血,采用ELISA法及流式细胞术检测观察对象血清及外周血淋巴细胞中的细胞毒性T淋巴细胞相关抗原4水平。结果与结论：细胞毒性T淋巴细胞相关抗原4在肾移植后急性排斥组、肾功能稳定组及健康对照组血清中的表达水平差异有显著性意义(F=70.008 1,P=0.000 0)。肾功能稳定组显著低于健康对照组(P=0.000 0),急性排斥组显著低于健康对照组(P=0.000 0),急性排斥组显著低于肾功能稳定组(P=0.000 0)。细胞毒性T淋巴细胞相关抗原4在肾移植后急性排斥组、肾功能稳定组及健康对照组淋巴细胞中的表达水平差异无显著性意义(F=1.865 6,P=0.161 7)。提示细胞毒性T淋巴细胞相关抗原4在肾移植患者发生排斥反应时血清中表达减低,具有一定的相关性,可能参与了排斥反应的发生。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

尿趋化因子IP-10和Fractalkine在移植肾急性排斥反应早期诊断中的应用

背景：相关研究已证实,趋化因子IP-10、Fractalkine在器官移植后急性排斥反应过程中发挥着重要的作用。 目的：检测尿液中IP-10和Fractalkine水平变化,并结合肾组织活检病理,探讨尿液中IP-10 和Fractalkine在移植肾急性排斥反应早期诊断中的意义。 方法：106例同种异体肾移植患者,根据移植后临床表现、实验室检查及肾穿刺组织病理学检查结果,分为急性排斥反应组(n=16)和非急性排斥反应组(n=90);另选择健康志愿者作为正常对照组。用双抗体夹心酶联免疫吸附试验检测尿IP-10和Fractalkine浓度变化。 结果与结论：急性和非急性排斥反应组患者在移植后的尿IP-10及Fractalkine的表达水平均较移植前明显升高,但非急性排斥反应组在移植后7 d呈下降趋势,至第11天降至移植前水平,而急性排斥反应组则持续高表达,IP-10在移植后第1天和Fractalkine在移植后第3天即与急性排斥反应组比较,差异有显著性意义(P < 0.05)。提示,肾移植后尿液中IP-10和Fractalkine水平的检测对于急性排斥反应发生的早期诊断和早期治疗具有重要意义。     

移植肾穿刺病理组织中抗体介导的排斥反应

背景：体液性排斥以激素耐受和难治性为其显著的特点,常常发生在免疫高敏的受者身上。 目的：对肾功能不全移植肾进行常规穿刺病理活检,根据病理诊断观察抗体介导性排斥反应的治疗效果,分析移植肾穿刺病理活检的安全性。 方法：选取肾移植后有移植肾穿刺活检指征的患者84例,在B超引导下应用BARD(美国)活检穿刺针行移植肾穿刺活检,活检组织行常规苏木精-伊红染色,组织化学染色,同时常规行C4d免疫组织化学染色,依据Banff’05标准进行病理分型,根据病理状态明确诊断进行相应的临床治疗,观察治疗效果。 结果与结论：84例患者除1例由于组织少难以诊断,其余病理诊断移植肾超急性排斥反应1例,急性抗体介导性排斥反应5例,慢性抗体介导性排斥反应2例,C4d免疫组织化学染色阳性16例。经过治疗8例抗体介导性排斥反应患者中4例移植肾功能得以恢复,3例未恢复,1例移植肾失功,移植肾切除。患者无不良反应发生。结果表明移植肾穿刺病理活检对移植肾无不良影响。     

Reduced CD40L expression on ex vivo activated CD4+ T-lymphocytes from patients with excellent renal allograft function measured with a rapid whole blood flow cytometry procedure

BACKGROUND: The CD40-CD40L (CD154) costimulatory pathway plays a critical role in the pathogenesis of kidney allograft rejection. In renal transplant biopsies, CD4+CD40L+ graft-infiltrating cells were detected during chronic rejection in contrast to acute rejection episodes. Using a rapid noninvasive FACS procedure, we were able to demonstrate CD40L upregulation in peripheral blood of patients with chronic renal allograft dysfunction. MATERIALS AND METHODS: Whole blood from recipients of renal allografts was stimulated with PMA and ionomycin and measured by flow cytometry. Patients were assigned to three groups based on transplant function. Group 1: 26 patients with excellent renal transplant function; group 2: 28 patients with impaired transplant function; group 3: 14 patients with chronic allograft dysfunction and group 4: 8 healthy controls. RESULTS: The median percentage +/- SEM of CD4+/CD40L+ cells stimulated ex vivo at 10 ng/ml PMA was as follows: group 1: 28.3 +/- 4.1%; group 2: 18.4 +/- 2.4%; group 3: 50.1 +/- 5.0% and group 4: 40.4 +/- 3.4%. Subdivisions of groups 2 and 3 resulted in different CD40L expression patterns. Patients with increased serum creatinine since the initial phase after transplantation (groups 2a and 3a) revealed a higher percentage of CD4+CD40L+ cells than patients showing a gradual increase over time (groups 2b and 3b). Consequently, patients of group 3a exhibited a significantly reduced transplant function compared with those of group 3b. CONCLUSION: After PMA + ionomycin stimulation, patients with excellent kidney graft function displayed significantly reduced expression of CD40L surface molecules on CD4+ cells early after transplantation. Those with a chronic dysfunction of the renal graft showed significantly more CD4+ cells expressing CD40L compared to the other transplanted groups. These results demonstrate that the percentage of CD4+CD40L+ cells stimulated ex vivo in peripheral blood may be a valuable marker for chronic allograft nephropathy.     

大鼠心脏移植排斥反应过程中外周血CD28、CD40通路相关分子的变化

目的探讨CD28、CD40共刺激通路与排斥反应的关系,同时也为排斥反应的诊断寻找一种新的检测指标。方法采用大鼠异位心脏移植模型,用免疫组化方法动态检测外周血单核细胞（PBMC）CD28、CTLA4、CD40及CD40L分子的表达。结果在0～4级排斥反应中,外周血细胞CD28分子阳性表达率在各组间的差异无统计学意义。外周血细胞表达CTLA4分子的阳性率随排斥反应增强而升高（P〈0.01）。CD40及CD40L在PBMC中的表达强度也随排斥反应的分级逐渐增强（P〈0.01）。结论外周血CTLA4、CD40及CD40L分子的表达与排斥反应有密切关系,动态检测这些分子有助于对排斥反应状态的评价。     

尸肾移植急性排斥反应与患者淋巴细胞CD62L、CD11a、CD4、CD8表达的关系

为探讨同种异体尸肾移植排斥反应病人淋巴细胞CD62L、CD11a表达与T细胞亚群及CD4/CD8的关系和意义。利用单克隆抗体 流式细胞仪荧光免疫技术 ,测定 10例肾移植排斥反应病人术后不同时间外周血淋巴细胞CD62L、CD11a、CD4、CD8表达并计算CD4/CD8。结果 ,肾移植病人排斥反应时其CD62L (4 6 1± 18 7vs 31 3± 10 5 ,P <0 0 1)、CD11a (4 9 5±2 0 2vs 31 9± 12 4,P <0 0 1)、CD4(2 4 4± 7 7vs 17 9± 7 4,P <0 0 1)、CD8(14 7± 2 9vs 10 4± 3 2 ,P <0 0 5 )表达均较排斥前明显增加 ,抗排斥治疗后CD11a (14 8± 6 2vs 49 5± 2 0 2 ,P <0 0 1)、CD4(15 8± 6 4vs 2 4 4± 7 7,P <0 0 5 )和CD4/CD8(1 2 8± 0 6vs 1 73± 0 79,P <0 0 5 )均明显下降。CD62L变化和CD8呈明显正相关 (r=0 9779,P <0 0 5 )。认为淋巴细胞CD62L、CD11a、CD4、CD8表达及CD4/CD8与肾移植排斥反应密切相关。免疫抑制剂 ,尤其甲基强的松尤能明显抑制淋巴细胞CD11a、CD4表达和CD4/CD8比值可能是其发挥抗排斥作用的重要机制。     

CD28/CTLA-4 and CD80/CD86 costimulatory molecules are mainly involved in acceptance or rejection of human liver transplant

CD28/CTLA-4 interactions with their specific B7-ligands (CD80 and CD86) have decisive roles in antigenic and allogenic responses. Recently, experimental transplant studies demonstrated that donor-specific tolerance is achieved by blocking these interactions. The present study analyzes the expression of these co-stimulatory molecules in peripheral blood cells from 74 liver recipients and in 16 liver biopsies, which were classified into acute-rejection (AR, n = 27) and nonacute-rejection (NAR, n = 47) groups, as well as their influence on the in vitro response of in vivo allosensitized cells. The results clearly indicate that in human liver transplant too, B7 and CD28/CTLA-4 expression on B and CD4(+) peripheral lymphocytes respectively, contributes to graft acceptance or rejection, and appears to be of crucial importance in modulating the host alloresponse and specific-CTL generation. In the NAR-group, costimulatory molecule expression remained at basal levels after transplant, whereas in the AR-group these molecules were significantly upregulated on days of AR. CTLA-4 was observed in the infiltrating lymphocytes in most of the biopsies, but CD80 or CD86 were not. Moreover, specific cytotoxicity from the in vivo primed cells was clearly suppressed in the NAR-patients with low co-stimulatory molecule expression, whereas this activity was not modified but rather stimulated in the AR-group. Together, these findings indicate that intervention of CD28/CTLA-4/B7 signaling could be therapeutically useful in clinical transplantation.     

Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine

BACKGROUND: Acute rejection is a serious and frequent complication of renal transplantation, and its diagnosis is contingent on the invasive procedure of allograft biopsy. A noninvasive diagnostic test for rejection could improve the outcome of transplantation. METHODS: We obtained 24 urine specimens from 22 renal-allograft recipients with a biopsy-confirmed episode of acute rejection and 127 samples from 63 recipients without evidence of acute rejection. RNA was isolated from the urinary cells. Messenger RNA (mRNA) encoding the cytotoxic proteins perforin and granzyme B and a constitutively expressed cyclophilin B gene were measured with the use of a competitive, quantitative polymerase chain reaction, and the level of expression was correlated with allograft status. RESULTS: The log-transformed mean (+/-SE) levels of perforin mRNA and granzyme B mRNA, which encode cytotoxic proteins, but not the levels of constitutively expressed cyclophiiin B mRNA, were higher in the urinary cells from the 22 patients with a biopsy-confirmed episode of acute rejection than in the 63 recipients without an episode of acute rejection (perforin, 1.4+/-0.3 vs. -0.6+/-0.2 fg per microgram of total RNA; P<0.001; and granzyme B, 1.2+/-0.3 vs. -0.9+/-0.2 fg per microgram of total RNA; P<0.001). Analysis involving the receiver-operating-characteristic curve demonstrated that acute rejection can be predicted with a sensitivity of 83 percent and a specificity of 83 percent with the use of a cutoff value of 0.9 fg of perforin mRNA per microgram of total RNA, and with a sensitivity of 79 percent and a specificity of 77 percent with the use of a cutoff value of 0.4 fg of granzyme B mRNA per microgram of total RNA. Sequential urine samples were obtained from 37 patients during the first nine days after transplantation; and measurements of the levels of mRNA that encoded cytotoxic proteins identified those in whom acute rejection developed. CONCLUSIONS: Measurement of mRNA encoding cytotoxic proteins in urinary cells offers a noninvasive means of diagnosing acute rejection of renal allografts.     

The role of B7-CD28 co-stimulation in tumor rejection

The role of B7 co-stimulatory signaling in in vivo tumor rejection remains incompletely characterized. In particular, the relative competence of B7-1 (CD80) and B7-2 (CD86) to provide effective co- stimulus is not well defined, and the identification of the T cell co- stimulatory receptor that mediates B7 co-stimulation in tumor rejection has not been addressed. These issues were studied by assessing rejection of B7-negative or B7-transfected tumor cells in CD28- expressing or CD28-deficient hosts. B7-negative EL4 tumor cells grew progressively in normal syngeneic C57BUL6 (B6) mice. In contrast EL4 cells transfected with either full length B7-1 or full length B7-2 were rejected, indicating that both B7-1 and B7-2 are competent to mediate rejection of EL4 tumor cells. Expression of truncated B7-1 or B7-2 products, with complete deletion of cytoplasmic domains, was as effective as expression of full length B7-1 or B7-2 in mediating rejection. In contrast to the rejection of B7-transfected EL4 cells observed in CD28-expressing syngeneic hosts, B7-1- and B7-2-positive EL4 cells as well as control EL4 cells grew progressively in CD28- deficient mice, demonstrating the requirement for host expression of CD28 in B7-mediated tumor rejection. These results indicate that interaction of host CD28 with co-stimulatory extracellular B7-1 or B7-2 ligands expressed on tumor cells can play a necessary role in mediating tumor rejection.      

Decreased humoral antibody episodes of acute renal allograft rejection in recipients expressing the HLA-DQβ1*0202 allele

The present investigation was designed to show the effect of human leukocyte antigen (HLA) class II molecular allelic specificities in the recipient on the induction of humoral antibody rejection, identified by C4d peritubular capillary staining, as well as specific antibody identified by Luminex technology. Major histocompatibility complex (MHC) class II molecules are expressed on dendritic cells, macrophages, and B lymphocytes and they present antigenic peptides to CD4 positive T lymphocytes. Human renal peritubular and glomerular capillaries express class II MHC molecules upon activation. Expression of class II molecules on renal microvascular endothelial cells exposes them to possible interaction with specific circulating antibodies. We hypothesize that HLA-DQβ1*0202 expression in recipients decreases the likelihood of antibody-mediated renal allograft rejection. We found that 80% (=25) of DQ2 positive haplotype recipients failed to induce humoral antibody renal allograft rejection and 20% (n=25) of DQ2 positive haplotype recipients induced humoral antibody renal allograft rejection (p=0.008). By contrast, 48% (n=46) of DQ2 negative haplotype recipients failed to induce a humoral antibody component of renal allograft rejection and 52% (n=46) of DQ2 negative haplotype recipients induced humoral antibody-mediated renal allograft rejection. Our results suggest that recipients who express the DQβ1*0202 allele are less likely to induce a humoral antibody component of acute renal allograft rejection than are those expressing DQ1, DQ3, or DQ4 alleles. DQβ1*0202 allele expression in recipients could possibly be protective against acute humoral allograft rejection and might serve as a future criterion in recipient selection and in appropriate therapy for acute renal rejection episodes.     

Thermostable erythrocyte rosettes in chronic renal failure and allograft rejection

Rejection of an allograft usually is preceded by activation of T lymphocytes, in which state such cells may be identified by their ability to form thermostable rosettes with sheep erythrocytes (TE-R). The objective of the present work, therefore, was to determine whether or not enumeration of TE-R in the peripheral blood was of any value in the diagnosis of rejection. The results showed no significant differences between TE-R (mean +/- SEM) in normal subjects (9.9 +/- 1.3; n = 25), renal allograft recipients without rejections (13.5 +/- 1.7; n = 5) and in patients who suffered from acute tubular necrosis in the posttransplant period (12.4 +/- 2.5; n = 8). In contrast, recipients who had rejection episodes showed a marked rise in TE-R levels (43.0 +/- 4.0; n = 11) about two to seven days prior to the diagnosis of rejection by clinical and chemical criteria. Furthermore, TE-R remained high if the rejection episodes turned out to be irreversible after therapy (42.2 +/- 3.7) but fell if the episodes were reversible (19.9 +/- 3.2). TE-R values were elevated in patients with chronic renal failure on maintenance hemodialysis (45.7 +/- 4.9; n = 23). Neither acute dialytic runs or acute infections altered TE-R values. In conclusion, those results show that enumeration of TE-R may be helpful in the early diagnosis of allograft rejection, before clinical and chemical stigmata are apparent.