肾移植受者HLA体液致敏因素

目的：探讨肾移植受HLA体液致敏的形成原因。方法：应用ELISA方法对199例（男133例,女66例）肾移植等候血中HLA抗体进行检测,分析与年龄、性别、透析时间、移植史、输血次数、妊娠史的关系。结果：HLA体液致敏的分布在女性组高于男性组（32％vs17％,P＜0．05）;在输血组高于无输血组（43％vs6％,P＜0．001）;在透析时间≥1a组高于透析时间＜1a组（43％vs20％,P＜0．05）;在有移植史组高于无移植史组（91％vs32％,P＜0．001）;在有妊娠组高于无妊娠组（40％vs8％,确切概率法P＝0．021）。结论：输血、移植、长期透析、妊娠是肾移植受致敏的重要因素。     

初次肾移植等候者中HLA体液致敏因素的分析

目的 分析多次输血、妊娠在初次肾移植等候者ＨＬＡ体液敏中的作用。方法 采用ＥＬＩＳＡ方法测定８６例初次肾移植等候者血清抗ＨＬＡＩｇＧ型抗体。结果 多次输血和妊娠患者中ＨＬＡ致敏率分别为６０％和６１％,而对照组中分别为３１％和１２．５％（Ｐ〈０．０５）结论 多次输血和妊娠是ＨＬＡ体液致敏的重要因素。     

HLA体液致敏与肾移植

目的：探讨肾移植受者HLA体液致敏的形成机制及其对肾移植术后排斥反应发生的影响，同时评价其对排斥反应的辅助诊断作用。方法：采用ELISA方法对199例次肾移植受者定期进行HLA抗体水平检测，分析其与患者的年龄、性别、透析时间、移植史、输血次数、孕次、冷缺血时间、热缺血时间、HLA体液致敏及HLA错配数、术后早期排斥反应的发生与恢复、肾功能延迟恢复的关系。结果：单因素分析显示性别、移植史、输血、妊娠、透析时间与HLA致敏相关（P＜0．05），致敏及HLA错配与排斥反应发生相关（P＜0．05）；而多因素分析提示移植史、输血与致敏相关，致敏及HLA错配与排斥反应发生相关，而且致敏与肾功能延迟恢复发生相关。HLA抗体水平升高和减低与排斥反应的发生和逆转呈正相关。结论：移植史、输血、妊娠和长期透析是移植受者HLA致敏的重要因素；致敏及HLA错配是排斥反应及肾功能延迟恢复的主要危险因素；HLA抗体水平检测对排斥反应的发生和逆转有辅助诊断作用。     

HLA配型与肾移植器官的分配

<正> 许多器官功能衰竭的患者,器官移植是惟一的解救途径。目前世界每年器官移植数目超过4万人,为20世纪70年代的3倍,但仍不能满足临床上的需求,1995年有3000余名患者因得不到器官移植而死亡。而获得器官移植的患者,一部分因各种因素的影响,移植的器官受到了排斥。我们分析了1995年至今1480例同种异体肾移植HLA配型与器官分配的情况,探讨了HLA配型技术以及根据HLA配型情况进行器官分配的可行性,为进一步研究HLA配型对肾移植的远期疗效提供了较可靠的依据。 所有病例移植前,除接受常规检查外,还要进行A、B、O血型检查,A、B、O血型系统是人体一大主要组织相容性系统,A、B、O血型抗原是一种组织相容性抗原,肾移植时,如果A、B、O血型不相配合,移植后立即发生超急性排斥反应。选择供者A、B、O血型的依据与输血的原则相同,血型相配后再进行HLA配型。进行供受者HLA-Ⅰ、Ⅱ类抗原单克隆抗体干板分     

肾移植中随机HLA配型的研究

目的 了解随机HLA配型的供－受配合率的多寡，为器官移植的广泛开展提供一些基础性资料。方法 对336例肾移植供－受随机的HLA－A、B和DR抗原配型进行分析。结果 HLA6个抗原完全错配率为24．40％（82／336），5个抗原错配率为33．33％（112／336），4个抗原错配率为27．68％（93／336），3个抗原错配率为11．91％（40／336），2个抗原错配率为2．68％（9／336），1个抗原错配率和0个抗原错配率为0。随机HLA－A、B和DR1个抗原配合的在HLA－A抗原为49．7％（167／336），B抗原为27．7％（93／336），DR抗原为31．8％（107／336）。2个抗原配合的在A抗原为4．76％（16／336），B抗原为2．08％（7／336），DR抗原为3．27％（11／336）。结论 完全配合的HLA抗原和5个HLA抗原配合的几率极低。在随机肾移植供－受中，HLA抗原A、B和DR抗原位点的2个等位基因完全配合的几率很低。     

肾移植中随机HLA配型的研究

为了解随机ＨＬＡ 配型的供 受者配合率的多寡,为器官移植的广泛开展提供一些基础性资料,对３３６ 例肾移植供 受者随机的ＨＬＡ Ａ、Ｂ 和ＤＲ 抗原配型做了分析。ＨＬＡ６ 个抗原完全错配率为２４ ．４０ ％ （８２／３３６） ,５ 个抗原错配率为３３ ．３３ ％ （１１２／３３６） ,４ 个抗原错配率为２７ ．６８ ％ （９３／３３６） ,３ 个抗原错配率为１１ ．９１ ％ （４０／３３６） ,２ 个抗原错配率为２ ．６８ ％ （９／３３６） ,１ 个抗原错配率和０ 个抗原错配率为０ 。随机ＨＬＡ Ａ、Ｂ 和ＤＲ１ 个抗原配合的在ＨＬＡ Ａ 抗原为４９ ．７ ％ （１６７／３３６） ,Ｂ 抗原为２７ ．７ ％ （９３／３３６） ,ＤＲ 抗原为３１ ．８ ％ （１０７／３３６） 。２ 个抗原配合的在Ａ 抗原为４ ．７６ ％ （１６／３３６） ,Ｂ 抗原为２ ．０８ ％ （７／３３６） ,ＤＲ 抗原为３ ．２７ ％ （１１／３３６） 。提示：完全配合的ＨＬＡ 抗原和５ 个ＨＬＡ 抗原配合的几率极低。在随机肾移植供 受者中,ＨＬＡ 抗原Ａ、Ｂ 和ＤＲ 抗原位点的２ 个等位基因完全配合的几率很低。     

人异体肾移植HLA配型291例次

1998年至2000年,本院共行人异体肾移植术291例次,全部按照HLA配型选择供受体,取得了较好的临床效果,报道如下。     

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。     

HLA配型在肾移植中的临床应用

我院自 2 0 0 0年 1月— 2 0 0 3年 1月共实施了13例HLA配型肾移植术 ,手术效果良好 ,无 1例发生超急及急性排斥反应。经长期随访 ,13例患者及移植肾均健康存活 ,各项生化指标正常 ,其中8例患者已重返工作岗位。现将HLA配型在肾移植中的临床应用情况报告如下。资料与方法1　一般资料本组肾移植受者共 13例 ,年龄 2 0岁～ 4 8岁 ,男性 6例 ,女性 7例 ;首次移植 11例 ,二次移植2例。尿毒症病因 :慢性肾小球肾炎 9例 ,慢性肾盂肾炎 2例 ,狼疮性肾炎 1例 ,多囊肾 1例。其中1例患者因多种原因致透析效果差 ,合并有大量腹水。术前 13例患者常规…     

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.     

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.     

肾移植术后急性体液性排斥反应的治疗

目的探讨肾移植术后急性体液性排斥反应的治疗方案。方法对12例肾移植术后的急性体液性排斥反应采用抗胸腺球蛋白（ATG，100mg／d&#215;5d）、血浆置换（PP，1～3次）和大剂量丙种球蛋白（IVIG，每周1．0g／kg，分2～3次静脉滴注）联合治疗。结果12例患者排斥反应均逆转。1例患者并发急性肾小管坏死。抗排斥治疗期间未发生严重感染性并发症。随访12～38个月，1例患者在术后16个月因慢性排斥反应恢复血液透析，其余患者移植肾功能良好。结论ATG联合PP—WIG能有效逆转肾移植术后急性体液性排斥反应，成功率高，并发症少。     

Rituximab induction therapy 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 renal transplantation following induction therapy with rituximab in highly sensitized kidney transplant recipients.

Methods  Seven highly sensitized kidney transplant recipients who underwent rituximab therapy from December 2008 to December 2009 were retrospectively analyzed. There were 3 men and 4 women, with a mean age of 38.5 years (range, 21–47 years). The duration of hemodialysis was 3–12 months, with a mean duration of 11 months. For 4 patients, this was the second transplant; the previous graft survival time was 2–11 years, with a mean survival time of 5.8 years. All the female recipients had history of multiple pregnancies, and all patients had previously received blood transfusions. All donors were men, with a mean age of 32.5 years (range, 25–37 years). In 2 of the 7 patients, both class I and class II of panel reactive antibody were high; the remaining 5 patients showed either high in class I or in class II of panel reactive antibody. The mean panel reactive antibody value was 31% for class I and 51% for class II respectively. The donors and the recipients had the same blood type, with low lymphocyte cytotoxicity ranging from 2% to 5%. The human leukocyte antigen (HLA) mismatch numbers were from 2 to 4. All patients received tacrolimus (0.1 mg∙kg^-1∙d^-1) and mycophenolate mofetil (750 mg twice per day) orally 3 days prior to surgery. All patients received a single dose of 600 mg rituximab (375 mg/m²) infusion on the day before surgery and polyclonal antibody (antithymocyte globulin) on the day of surgery. Postoperative creatinine, creatinine clearance rate, and occurrence of rejection by pathological biopsy confirmation were monitored.

Results  No patient had delayed graft function after surgery. Two patients had acute rejection, one on day 7 and the other on day 13 post-surgery. Diagnosis of acute rejections was based on the clinical assessments and pathological biopsy results. According to the Banff 07 classification of renal allograft pathology, one of the patients was Ia and the other was IIa; the C4d staining was negative in both patients. One patient received methylprednisolone plus cyclophosphamide and the other received antithymocyte globulin (ATG) therapy, both leading to successful reversion of the acute rejection. All patients were discharged postoperatively and all had normal renal function during the 7th to 12th month follow-up. Pulmonary infection occurred in 1 patient 4 months after surgery and was successfully cured.

Conclusion  Rituximab induction therapy can reduce the occurrence of postoperative humoral rejection in highly sensitized renal transplant recipients, suggesting that kidney transplantation may be safe and effective for these patients.

     

Alemtuzumab induction therapy in highly sensitized kidney transplant recipients

Background  Immunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody, was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients.

Methods  In this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients (panel reactive antibody >20%). They were divided into two groups: alemtuzumab group (trial group) and anti-thymocyte globulin (ATG) group (control group). Patients in the alemtuzumab group received intravenous alemtuzumab (15 mg) as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab (15 mg) was given. The control group received a bolus of rabbit ATG (9 mg/kg), which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil (MMF). Acute rejection (AR) and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up. χ² test, t test and Kaplan-Meier analysis were performed with SPSS17.0 software.

Results  Median follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar (P >0.05). White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months (P <0.05). One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary infection or cardiac and pulmonary failure. Cumulative 2-year graft survival rate was 90.9% in the alemtuzumab group and 81.8% in ATG group (P >0.05) respectively. There was one graft failure in the alemtuzumab group and two graft failures in ATG group, with all graft failures at tributed to rejection episodes. The alemtuzumab group had a 2-year cumulative freedom from rejection rate of 81.8%, compared with 72.7% for the ATG group (P >0.05).

Conclusion  Alemtuzumab induction therapy for highly sensitized kidney transplant recipients is an effective and safe protocol yielding an acceptable acute rejection rate.

     

HLA alleles in patients with Guillain-Barre syndrome

ＧｕｉｌｌａｉｎＢａｒｒｅｓｙｎｄｒｏｍｅ(ＧＢＳ)ｉｓａｃｏｍｍｏｎｎｅｕｒｏｌｏｇｉｃａｌｄｉｓｅａｓｅｗｉｔｈｃｈａｒａｃｔｅｒｉｓｔｉｃｓｏｆｆｌａｃｃｉｄｐａｒａｌｙｓｉｓＴｈｅｅｔｉｏｌｏｇｙｏｆＧＢＳｉｓｔｈｏｕｇｈｔｔｏｂｅｄｅｍｙｅｌｉｎａｔｉｏｎａｎｄａｘｏｎａｌｄａｍａｇｅｓａｆｔｅｒｉｎｆｅｃｔｉｏｎＴｈｅｅｘａｃｔｍｅｃｈａｎｉｓｍｉｓｓｔｉｌｌｕｎｃｌｅａｒＭｏｌｅｃｕｌａｒｍｉｍｉｃｒｙｈｙｐｏｔｈｅｓｉｓｏｆＧＢＳｉｓｔｈｅｍｏｓｔｃｉｔｅｄｅｘｐｌａｎａｔｉｏｎＴ…     

Superiority of B locus matching over other HLA matching in renal graft survival

Graft survival after 348 consecutive first cadaver-donor renal transplants was significantly improved by HLA matching when recipients who had received pretransplant blood transfusions were matched with their kidney donor for two HLA-B locus antigens. No other type of HLA matching significantly improved graft survival in transfused recipients nor did any type of HLA matching in non-transfused recipients. Matching for one HLA-DR antigen had no benefit in transfused recipients. Only two patients received kidneys matched for both DR antigens and only two of those in whom DR matching had been performed had not been transfused. These results indicate that pretransplant blood transfusion and selection of graft recipients predominantly on the basis of HLA-B matching has significantly reduced the renal graft rejection rate in Newcastle upon Tyne over two years. Thus, HLA-B antigen matching should be adopted as the main criterion for kidney sharing between transplant centres.     

肾移植术后结核病18例回顾性临床分析

目的提高对肾移植术后合并结核病的认识。方法对近5年来肾移植术后结核病18例进行回顾性分析。结果肺结核16例,合并肺外结核3例,气管内膜结核2例,症状缺乏特异性。主要通过X线平片、反复痰中找抗酸杆菌、PCR查结核杆菌DNA、穿刺活检明确诊断。有4人合并其他病原体感染。经过正规抗结核治疗后治愈16人,死亡2人。不良反应主要是肝、肾功能损害,通过调整免疫抑制剂方案,肝、肾功能可恢复正常。结论肾移植术后结核感染发生率明显增高,正规抗结核治疗有效,但需要密切监测肝、肾功能的变化,及时调整免疫抑制剂方案。     

Protein A immunoadsorption therapy in the highly sensitized kidney transplant candidates

Background  Sensitization in transplant candidates increases risk of irreversible immunologic injury of graft in the early period postoperatively. Elimination of anti-human leukocyte antigen (HLA) antibodies using protein A immunoadsorption (IA) might benefit these patients.

Methods  Protein A IA was used in 21 patients with high panel reactive antibody (PRA). The patients had IA 1–6 times (median 5 times) with the interval period was 2–5 days (median 2.5 days).

Results  Total 67 IA procedures were carried out smoothly in all patients. IA treatment reduced PRA I (pre (31.4±3.8)% vs. post (24.4±3.4)%, P <0.01) and II (pre (37.1±4.3)% vs. post (34.1±3.9)%, P <0.01). However, PRA did not change in some patients after the treatment. The serum immunoglobulin (IgG, IgM and IgA) and complement C3, C4 level were decreased significantly. Hemoglobin and albumin levels were slightly decreased associated with IA procedures. Flu-like symptoms were observed in a few of cases during the procedure but generally mild and transient.

Conclusion  Protein A IA is capable to efficiently remove serum immunoglobulin and complement, reduce HLA class I and class II PRA in high sensitized transplant candidates, which is likely to benefit the kidney transplantation in these patients.

     

肾移植术后结核感染的临床分析

目的探讨肾移植术后并发结核感染的临床特点、诊断和治疗方案.方法回顾性分析13例肾移植术后并发结核感染患者的临床资料.结果 13例结核感染中肺结核12例,淋巴结结核1例.主要通过X线照片、反复痰中找抗酸杆菌、PCR查结核杆菌DNA、穿刺活检明确诊断.有4人合并其他病原体感染.经过正规抗结核治疗后治愈11人,死亡2人.不良反应主要是肝、肾功能损害,通过调整免疫抑制剂方案,肝、肾功能可恢复正常.结论肾移植术后结核感染发生率明显增高,正规抗结核治疗有效,但需要密切监测肝、肾功能的变化,及时调整免疫抑制方案.     

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.