肾移植受者群体反应性抗体监测的临床意义

目的 分析群体反应性抗体（PRA）监测对预测肾移植受者排斥反应发生的意义及探讨对高水平PRA受者的临床处理.方法 应用酶联免疫吸附分析法（ELISA法）动态监测肾移植受者的PRA水平,以PRA≥10%为阳性,10%≤PRA＜50%为低致敏、PRA≥50%为高致敏,并对37例术前高致敏患者行血浆置换.结果 1527例肾移植受者中,PRA阳性350例（22.9% ）,其中高致敏 94例（26.8% ）;PRA阳性组排斥反应发生率（21.1% ）高于PRA阴性组（3.8% , P〈0.01）, 术后PRA转为阳性组排斥反应发生率高于PRA无变化组（P〈0.01）,行血浆置换受者与未行血浆置换受者排斥反应发生率无差异（P〉0.05）,接受过移植、多次妊娠、多次输血受者易致敏,HLA-A、B、DR配型错配抗原〉3个受者急性排斥的发生率（16.9% ）明显高于错配抗原≤3个受者（1.7% , P〈0.01）.结论 动态监测PRA水平有助于预测排斥反应的发生.     

肾移植受者HLA特异性抗体的监测及临床应用

目的：探讨人类白细胞抗原（HLA）群体反应性抗体（PRA）对肾脏移植效果的影响。方法：采用酶联免疫吸附法（ELISA）和微量补体依赖性细胞毒试验（CDC）对897例例次肾移植受者的PRA进行动态监测。结果856例初次肾移植受者中术前PRA阳性者121例,占11％,而33例次2次移植和8次3次移植受者术前PRA阳性分别为58％和87％,与初次肾移植受者组比较,PRA阳性受者比例均显著增高（P＜0．001）。PRA阳性组受者肾移植术后排斥发生率为40％,而阴性组受者仅17％,两组比较有显著性（P＜0．01）。PRA阳性组受者的移植物存活率则明显低于阴性组（P＜0．001）,尤其是PRA＞40％的高效敏受者的1、3、5年和7年多移植物存活率与阴性组比较分别下降了24％、38％、57％和56％,均为P＜0．001。ELISA法与CDC法的双盲试验发现,319份受者血清中CDC－PRA的假阳性和假阴性率分别为3．8％和3．1％。结论PRA是预测受者致敏状态的敏感指标,对移植后排斥反应和移植物存活率均有明显影响。     

致敏肾移植受者主要组织相容性复合物I类链相关基因A抗体表达对预后的影响

目的 探讨致敏肾移植受者(群体反应性抗体PRA>20%)主要组织相容性复合物I类链相关基因A抗体（MICA-Ab）的表达对患者预后的影响。 方法 收集本院2007年8月至2010年4月行肾移植的致敏受者51例,其中29例接受蛋白A免疫吸附,并在吸附前后行MICA-Ab检查;另22例未接受免疫吸附,在入院时行MICA-Ab检查。回顾分析移植受者人类白细胞抗原（HLA）、急性排斥反应、术后1周和4周Scr水平与MICA-Ab的关系。 结果 51例受者中16例MICA-Ab表达阳性（31.4%）,MICA-Ab表达阴性与阳性受者的急性排斥发生比例差异无统计学意义。PRA>40%受者的MICA-Ab表达显著高于PRA≤40%受者（P < 0.05）。HLA错配对MICA-Ab表达无显著影响。在接受免疫吸附受者中,MICA-Ab阳性组和阴性组出院时Scr水平差异无统计学意义;未接受免疫吸附受者情况相似。MICA-Ab水平在蛋白A免疫吸附后显著下降。 结论 MICA-Ab在致敏受者中表达升高,然而对受者预后无显著影响。蛋白A免疫吸附可有效去除致敏受者体内MICA-Ab。     

高度致敏肾移植受者的HLA抗体公共表位分析

目的：探讨对高度致敏肾移植受体进行人类白细胞抗原（HLA）特异性抗体的公共表位分析的临床意义。方法：对24例高度致敏受者（HLA－I类抗体PRA＞50％），作群全反应性抗体（PRA）的连续监测，并做抗体特异性鉴定和抗体公共表位分析。结果：24例高度致敏受者中21例（87．5％）具有公共表位抗体，抗体公共表位分析比抗体特异性鉴定能更准确反映抗体谱，16例高度致敏患者根据抗体公共表位分析结果找到HLA相容的供肾，成功地进行了肾移植术，结论：对少数高频率高免疫原性氨基酸残基公共表位的致敏是高敏受者致敏的主要原因，高度 致敏受者的,抗体公共表位分析能有效指导HLA配型。     

免疫吸附预防高致敏肾移植受者超急性排斥反应

目的探讨免疫吸附对高致敏‘肾移植受者超急性排斥反应的预防作用。方法对10例群体反应抗体（PRA）〉40％的‘肾移植受者术前行免疫吸附治疗，观察其超急性排斥反应发生情况及不良反应。结果10例高致敏肾移植受者均未发生超急性排斥反应，仅有2例发生急性排斥反应，并通过免疫吸附及调整免疫抑制剂得到逆转。所有受者随访至今移植‘肾功能良好，未发生排斥反应。结论免疫吸附可以安全、有效地预防高致敏人群‘肾移植术后超急性排斥反应。     

交叉反应组配型在高致敏患者肾移植中的应用

目的 探讨交叉反应组(CBEG)配型在高致敏患者肾移植中的临床意义。方法 动态监测肾移植受者体内群体反应性抗体(PRA)的水平及其特异性，按照CREG配型原则选择最匹配的供者。结果 60例受者术前PRA超过11％，均有单纯性或混合性升高；按照CREG配型，0～1个抗原错配、2个抗原错配、3～4个抗原错配者术后肌酐恢复正常的时间平均为6．5d、7．0d、12．7d，发生肾功能恢复延迟的例数分别为0、7例、3例，各组间的差异具有显著性(P＜0．05)。结论 高致敏受者在肾移植时采用CREG配型，可避开受者预存的HLA抗体特异性所对应的抗原，对于提高肾移植人／肾存活率具有重要意义。     

致敏受者移植肾存活率和抗HLA抗体的临床观察

目的观察致敏受者与非致敏受者移植肾存活率的差别,以及移植肾功能与抗HLA抗体变化的关系。方法纳入中山大学附属第一医院器官移植中心2000年4月至2008年12月间行肾移植后资料完整受者1309例。根据受者术前ELISA检测群体反应性抗体（PRA）的结果将受者分为50%≤PRA≤100%组（n=35）、10%≤PRA〈50%组（n=47）和PRA〈10%组（n=1227）。所有供受者采用PCR序列特异性引物进行HLA分型。运用标准HLA配型和氨基酸残基配型。采用Kaplan-Meier法对3组受者术后存活率进行组间生存分析。分析肾移植后抗HLA抗体的变化及其与移植肾功能和HLA错配的关系。结果随着随访时间增加,3组移植肾累积存活率均有下降。在术后3年内3组移植肾存活率差异较小（P〉0.05）,3年后3组移植肾存活率差异有统计学意义（P〈0.05）。10%≤PRA≤100%受者移植肾累积存活率显著低于PRA〈10%受者（P〈0.05）,50%≤PRA≤100%受者移植肾累积存活率也显著低于10%≤PRA〈50%受者（P〈0.05）。12例移植肾失功的受者中7例（58.3%）出现抗体增强,62例移植肾功能正常的受者中仅8例（12.9%）出现抗体增强,两者差异有统计学意义（P〈0.05）。出现新生抗体的受者抗体谱中,大多数包含有针对错配抗原的抗HLA抗体。结论无论是供者特异性还是非供者特异性抗体,抗HLA抗体的存在及其效价都会影响移植肾的存活。术后抗HLA抗体的变化与移植肾功能有关。     

高致敏肾移植受者行单次免疫吸附治疗的临床观察

我院自2001年12月至2003年12月共为22例高致敏受者在肾移植前行单次强化免疫吸附（IA）治疗，受者均在治疗后48h内行肾移植手术，预后良好，总结如下。     

群体反应性抗体检测在肾移植中的应用

目的 了解肾移植受者的ＨＬＡ体液致敏状态及致敏者受者的ＨＬＡ抗体特异性,筛选合适供者。方法 应用配组淋巴细胞板通过微量补体依赖淋巴细胞毒试验检测６２３例患者的群体反应性抗体（ＰＲＡ）。结果 肾移植受者中ＰＲＡ阳性受者占１１．５％,致敏受者移植后排斥反应发生率明显高于非致敏受者（Ｐ〈０．０１）,而移植物存活率则显著低于非致敏受者（Ｐ〈０．０１）。移植后ＰＲＡ水平升高级的排斥发生率和移植物丢失率殚显著     

HLA配型对群体反应性抗体阳性的肾移植受者人/肾存活率的影响

目的探讨HLA交叉反应组（CREGs）配型对群体反应性抗体（PRA）阳性肾移植受者人／肾存活率的影响。方法应用美国莱姆德公司LAT1240、LM720R、SSP2LB试剂，准确检测112例PRA阳性肾移植受者体内PRA的水平及其抗体的特异性，评估其致敏状态，应用CREGs配型标准选择最匹配的供者。结果112例受者中，HLA-Ⅰ类抗体阳性43例，Ⅱ类抗体阳性39例，Ⅰ、Ⅱ类抗体均为阳性30例；HLA配型0～5个位点错配数分别为6、39、38、21、7、1例，术后移植肾发生加速性排斥反应2例、急性排斥反应18例、慢性排斥反应5例、移植肾功能延迟恢复（DGF）4例，因排斥反应导致移植肾切除1例，死亡13例（其中移植肾带功能死亡5例）。目前人存活99例，肾存活96例，5年、3年和1年肾存活率分别为86．21％、86．96％和91．96％。结论运用CREGs配型原则，能使供、受者间的HLA相配率显著提高，可减少PRA对肾移植的不良影响，提高PRA阳性受者的人／肾存活率。     

Different responses of human anti-HLA and anti-αgal antibody to long-term intravenous immunoglobulin therapy

Concentrated human immunoglobulin (IVIG) has been administered intravenously in the treatment of autoimmune disorders and to reduce anti-HLA antibodies in highly sensitized patients awaiting organ transplantation. It has also been shown, in experimental animals, to prevent the hyperacute rejection of discordant xenografts, possibly by anticomplement activity. The aim of the present study was to assess the effect of IVIG therapy on both acquired anti-HLA antibodies and natural antigalactose α1–3 galactose (αGal) antibodies in five patients awaiting heart transplantation. Five patients placed on mechanical circulatory support who had developed high HLA panel-reactive antibodies (PRA) or in whom the percentage of PRA was increasing rapidly were treated weekly with 500 mg/kg IVIG, which contained 1% of anti-αGal IgG. Levels of PRA, anti-αGal IgG and IgM, and serum cytotoxicity to pig cells were measured before, during, and after therapy. PRA percentages in the five patients were initially 85%, 53%, 23%, 19% and 19% (mean 39%). Mean PRA fell by 66% after 3 months of therapy (to a mean PRA of 14%), and by 96% after 6 months therapy (to a mean PRA of 2%). Anti-αGal antibody levels and serum cytotoxicity to pig aortic endothelial cells did not change significantly. These results confirm the effectiveness of IVIG therapy in reducing PRA in HLA highly sensitized patients. It is likely that IVIG does not contain the relevant anti-HLA antibody, resulting in an accelerated catabolism of native alloantibodies. However, as IVIG contains a normal level of anti-αGal IgG, catabolism of anti-αGal IgG is not modified, as it is being continuously replaced. To achieve a decrease in the anti-αGal IgG level it would be necessary to use IVIG depleted of this antibody.     

后腹腔镜输尿管切开取石术对机体免疫功能的影响

目的:研究后腹腔镜输尿管切开取石术对机体免疫功能的影响。方法:60例输尿管切开取石术患者随机分为后腹腔镜组(30例)和传统开放手术组(30例),患者术前、手术开始后2h、术后1d、术后2d、术后8d抽取静脉血8ml,T细胞亚群CD4、CD8应用Elite-ESP型流式细胞仪进行分析检测,血清免疫球蛋白IgA、IgG、IgM水平采用免疫速率散射比浊法检测。结果:本研究提示腹腔镜组CD4、CD8手术后下降程度较小,且恢复较快,术后8d均恢复至术前水平。开放手术组术后CD4、CD8下降程度较大,恢复较慢,术后8d仍较术前和腹腔镜组低(P0.05)。腹腔镜组IgA、IgG、IgM术后各个时间节点较术前均无差异(P0.05)。开放手术组IgM术后各个时间节点较术前均无差异;IgG术后1d开始下降,术后8d仍未恢复;IgA术后下降较迟,术后8d开始低于术前水平(P0.05)。结论:后腹腔镜输尿管切开取石术与开放手术比较,其对机体细胞免疫和体液免疫功能影响较小,体现了微创优势。     

Removal of lymphocytotoxic antibodies by pretransplant immunoadsorption therapy in highly sensitized renal transplant recipients

A high level of panel-reactive antibodies (PRA) in potential renal transplant recipients is associated with a long waiting time until transplantation and correlates inversely with graft outcome. We report our experience with the employment of immunoadsorption (IA) using a column composed to sepharose-bound staphylococcal protein A (which has a relatively selective affinity for binding IgG compared with other immunoglobulins) to decrease the PRA levels and expedite transplantation in 6 highly sensitized potential renal transplant recipients (1 primary and 5 awaiting second transplants). All patients had PRA levels of greater than or equal to 70% for a duration of 1 year prior to IA. Only patients with antibody specificity localized to 1 or 2 HLA A or B antigens were accepted for the study. IA procedures were performed on alternate days until a twofold decrease in antibody titer had occurred (maximum: 6 procedures). Repeat procedures were initiated if the HLA antibody titer returned to its baseline value. Intravenous cyclophosphamide (CY) (10 mg/kg/day every 3 weeks) and methylprednisolone (MP) (0.5 mg/kg/day) were provided as adjunctive immunosuppression until transplantation. A total of 44 immunoadsorption procedures were performed (27 primary and 17 repeat) with treatment of 2.49 +/- 0.02 plasma volumes per session. Serum IgG concentration decreased 95 +/- 3% and PRA activity decreased 75 +/- 16% after the primary treatment course. Four patients received cadaveric grafts within 3.7 +/- 1.2 months following the last IA procedure. Three grafts are functioning at 1 year, 8 months, and 8 weeks posttransplant. The remaining graft demonstrated primary nonfunction. All four patients had a past positive crossmatch using pre-IA sera with their respective donors. Patients not transplanted exhibited rapid resynthesis of IgG and a return of the PRA towards baseline levels within a few weeks after IA. We conclude that IA can effectively remove HLA antibodies and expedite graft availability in highly sensitized patients.     

EV71感染的手足口病患儿体液免疫临床分析

目的探讨并分析EV71感染手足病患儿体液免疫状况。方法分别测定30例EV71阳性和30例EV71阴性的手足口病患儿与同期20例健康儿童的血清IgG、IgA、IgM及补体C3、C4水平,采用SPSS18.0软件用t检验统计分析EV71阳性组的IgG、IgA、IgM及补体C3、C4水平与EV71阴性组和对照组各项指标水平的差异。结果 EV71阳性组和阴性组手足口病患儿各指标水平无显著差异;与对照组相比,EV71阳性组患儿血清IgG、IgA、C3、C4水平降低（P〈0.05）;IgM明显升高（P〈0.001）。结论 EV71感染的手足口病患儿存在体液免疫功能紊乱,但EV71感染对体液免疫功能影响无显著特异性。     

Immunoadsorption of sensitized kidney transplant candidates immediately prior to surgery

Patients with anti-human leucocyte antigen (HLA) antibodies from previous transplantation, blood transfusion are highly sensitized and at risk to hyperacute renal graft loss. As these antibodies are identified to be of pathogenic importance, an effective removal may allow successful transplantation. Six 'high risk patients' [panel-reactive antibodies (PRA) >30% or retransplanted patients with an acutely rejected first graft within 6 months from surgery] were treated by protein A immunoadsorption (IA) immediately prior to transplantation. We treated the calculated plasma volume one to three times prior to surgery: mean 4600 mL (range 2100-10 200 mL). After transplantation we repeated the sessions according to antibody (Ab) recurrence, graft function and signs of rejection. The panel reactive Ab were reduced from mean 65% pre-IA (range 35-85) to lowest 15% (range 0-55). After the course they reappeared to 30% (range 0-90). Five of the six patients had no clinical signs of vascular rejection. At a follow-up of mean 54 months (+/-14) four grafts still function with a mean serum creatinine of 172 micromol/L (+/-57). Protein A IA is a safe and effective adjunct in the treatment of highly sensitized patients awaiting renal transplantation. The treatment immediately prior to operation can prevent hyperacute rejection and increases the graft survival in these patients.     

Contributions and clinical significance of IgM and autoantibodies in highly sensitized renal allograft recipients

The contributions of auto and IgM antibodies in the levels of serologic reactivities of 30 highly sensitized patients were assessed by autologous T cell crossmatches at 4 degrees C and 22 degrees C and dithiothreitol (DTT) reduction of IgM antibodies. The range of panel reactivities of sera from these patients was 30-100%, median 55%. A monthly screen of these sera against a 30-member T cell panel was performed with and without addition of DTT (final concentration = 0.005 M). The results were divided into 3 groups. Group 1 consisted of 17 sera whose PRA values did not change following the DTT treatment. Also none of these sera had autoantibodies, suggesting that these sera contained DTT-resistant (IgG) antibodies, most likely directed against allogeneic targets. Group 2 consisted of 10 sera whose PRA values declined substantially (20-42%) following the DTT treatment, but only 1 serum derived from a patient with systemic lupus erythematosus had autoantibodies. These results suggested that although these sera contained IgM and IgG antibodies, these antibodies were most likely directed at allogeneic target structures with only one exception. Group 3 consisted of 3 sera that became completely unreactive to panel lymphocytes following the DTT treatment. All 3 sera had autoantibodies that were also removed with DTT, suggesting that these sera contained predominantly IgM antibodies directed at autologous target cells. All 3 patients from whom these sera were derived received successful kidney transplants across donor-specific positive T cell crossmatches that became negative following the DTT treatment. We conclude that although 13 out of 30 patients have IgM antibodies, only a small subset of these patients have autoantibodies. Renal transplantation in the presence of auto/IgM antibodies may be safe.     

IgA肾病患者尿蛋白成分与临床病理指标的相关性

目的：探讨IgA肾病（IgAN）患者尿中白蛋白（Alb）、转铁蛋白（TRF）、免疫球蛋白（IgG）、α1-微球蛋白（α1-MG）、β2-微球蛋白（β2-MG）与临床及病理指标的关系。方法：采集143例原发性IgAN患者肾穿刺前新鲜晨尿,用免疫散射比浊法检测Alb、TRF、IgG、α1-MG、β2-MG的浓度;收集患者血压、血肌酐、24h尿蛋白定量以及病理分级、肾小球病变积分、肾小管间质损害积分、血管病变等资料,并进行对比分析。结果：143例IgAN患者,尿Alb、TRF、IgG、α1-MG、β2-MG升高的比例分别为95.8%、100%、91.6%、63.6%、74.1%。IgAN患者血压升高组较血压正常组尿Alb、IgG、α1-MG明显升高;肾功能异常组较肾功能正常组尿IgG、α1-MG、β2-MG明显升高。随病理Lee氏分级、肾小球硬化程度、肾小管间质损害加重,尿Alb、IgG、α1-MG明显升高;随肾小球系膜增殖程度加重,尿Alb、IgG、α1-MG以及TRF明显升高;随血管病变出现,尿α1-MG明显升高。结论：IgAN患者尿Alb、TRF、IgG、α1-MG、β2-MG与多种反应疾病进展的临床及病理指标变化一致而又各有侧重,可以更全面地反映IgAN患者肾脏病变的程度,对判断病情、随访疗效具有一定的实际意义。     

原发性IgA肾病与非IgA系膜增生性肾小球肾炎的临床病理分析

目的 比较原发性IgA肾病与非IgA系膜增生性肾小球肾炎（non-IgA mesangial proliferative glomerulonephritis,non-IgA MsPGN）的临床及肾脏病理改变特点.方法 选择我科经肾活检确诊的原发性IgA肾病患者（A组）和non-IgA MsPGN患者（B组）进行临床与病理资料对比分析.结果 A、B组的性别、前驱上呼吸道感染诱因、起病时伴发高血压、镜下血尿、血肌酐无统计学差异（P＞0.05）.B组较A组起病年龄小,起病时伴发肉眼血尿比率低,肾病综合征发生率高,血IgG水平低,差异均有统计学意义（P＜0.05）.A组肾小球、肾小管间质、肾小动脉病理改变发生率高于B组（P＜0.05）,IgM、C3沉积、系膜区电子致密物沉积、大块状致密物、足细胞微绒毛化、肾小球基底膜分层发生率均较B组高（P＜0.01）.结论 IgA肾病与non-IgA MsPGN在临床表现、病理改变上存在明显差异,IgA肾病较non-IgA MsPGN病理损伤重.