抗供体移植特异性抗体与肾移植排斥的相关性研究

为探讨抗供体特异性抗体与同种异体肾移植间移植物排斥的关系。用ＨＬＡ位点氨基酸残基配对检测法（ＥＬＩＳＡ－ＬＡＴ－Ｍ和ＥＬＩＳＡ－ＬＡＴ－ＩＤ）,对１６６例血清分为ＡＲ,ＣＲ和正常对照共３组进行筛选测定。按ＬＡＴ酶联检测试剂盒要求操作抗体特异性的确定根据阳性结果的反应格局综合判断,结果显示抗ＨＬＡⅡ类ＩｇＧ抗体阳性率分别为ＡＲ３８％,ＣＲ３７％正常２．３％。（Ｐ〈０．０１）,Ⅱ类抗体与急,慢性排斥反     

SARS患者及其医护人员血中特异IgG抗体变化规律的初步研究

目的:对临床诊断严重急性呼吸道综合征(Severe Acute Respiratory Syndrome, SARS,即非典型肺炎)患者血抗SARS冠状病毒IgG抗体的变化规律和密切接触SARS 患者的医护人员有无隐性感染作初步调查.方法:用酶联免疫吸附测定(ELISA)检测57例正常人、127例在SARS病房工作1个月的医护人员和73例不同病程SARS患者血浆抗SARS冠状病毒IgG抗体的水平.结果:正常人和医护人员血浆中尚未检测到抗SARS冠状病毒IgG抗体.SARS患者发病第0～7、8～10、11～14、15～20天后血浆中抗SARS冠状病毒IgG抗体的阳性率分别为0、33%、52%和86%,总阳性率为61%.结论:ELISA检测血浆中抗SARS冠状病毒IgG抗体的特异性和敏感度均很好.呈阳性反应病例可确诊已受病毒感染,对于发病早期还未产生抗体的病人,阴性结果不能说明未受感染,应做进一步观察.本组资料提示SARS可能不具有隐性感染性.     

活体肾移植体液性排斥反应与抗HLA抗体的研究

目的研究活体肾移植术后体液性排斥反应与抗HLA抗体及其特异性的关系。方法87例活体肾移植患者,分别于肾移植术前1天及术后6个月行流式细胞法群体反应抗体检测(Flow PRA screening test)。同时应用独立抗原免疫磁珠分析法(LAB Single antigen analysis)检测抗HLA抗体的特异性。全部患者于术中、术后两周、术后6个月和1年4个时间段进行移植肾穿刺病理检查。结合患者一般情况、病理诊断及抗HLA抗体检测结果,在体液性排斥反应发生率、预后、相关抗体种类及特异性等方面进行回顾性分析。结果87例患者中,群体反应抗体(PRA)术前1天检测结果均为阴性。术后6个月时28例(32.2%,28/87)为阳性。其中,15例(53.6%,15/28)为非供体特异性抗HLA抗体;13例(46.4%,13/28)存在供体特异性抗体。病理结果提示,供体特异性抗体患者中11例(84.6%,11/13)在术后6个月内出现了严重的抗体介导的体液性排斥反应;术后1年时仍然有5例持续存在体液性排斥,移植肾3年内完全丧失功能,恢复到规律透析状态。非供体特异性抗体患者术后无体液性排斥反应发生。术后抗HLA抗体阴性组与阳性组3年移植肾存活率分别为96.6%和75.0%。结论活体肾移植患者抗HLA抗体的出现与术后急性体液性排斥反应的发生明显相关,特别是术后出现供体特异性抗HLA抗体的患者急性体液性排斥反应的发生率更高,预后更差。肾移植术后严密监测抗HLA抗体的出现对于及时调整免疫抑制方案改善移植肾长期存活具有重要意义。     

类风湿关节炎患者Ⅱ型胶原特异性T细胞增殖及抗体生成与HLA-DR4的关系

目的　探讨类风湿关节炎(RA)患者Ⅱ型胶原 (CⅡ)特异性T细胞增殖和CⅡ抗体生成,及与人类白细胞抗原(HLA)- DR_4亚型之间的关系。方法　将CⅡ263 -272十肽与 62例RA患者外周血单个核细胞(PBMC)共孵育 5d,应用四甲基偶氮唑盐法测定T细胞增殖。酶联免疫吸附试验(ELISA)法测定患者血清CⅡ抗体水平。提取 40例患者外周血基因组DNA,以 33种HLA- DR_4等位基因亚型的特异引物PCR扩增后测定患者HLA DR分型情况。结果　在 62例RA患者中, 38例(61 .3% )患者的T细胞在加入CⅡ263- 272后出现明显增殖,CⅡ263 -272抗体阳性率为 53. 2%。细胞增殖反应阳性的患者CⅡ263- 272抗体的阳性率为 66. 7%,增殖反应阴性的患者为 34 6%,两者比较P<0 .05。CⅡ263 -272抗体阳性的患者T细胞增殖反应率为 69 7%,阴性患者为 42 .1%, 两者比较P<0 .05。所有患者T细胞增殖刺激指数 (SI)与CⅡ263- 272抗体浓度呈显著正相关 (r=0 68,P<0. 01)。40例患者HLA分型中,有 16例携带HLA -DR_4等位基因,未发现HLA DR_4与CⅡ特异性T细胞增殖反应、CⅡ抗体阳性有显著相关性。结论　CⅡ抗体的生成可能与CⅡ特异性T细胞介导的B细胞活化有关。     

类风湿关节炎患者抗人、猪两种属Ⅱ型胶原抗体检测的意义

目的 :检测类风湿关节炎 (RA)患者血清中人及猪Ⅱ型胶原抗体水平 ,探讨其在RA发病中的意义。方法 :用自提取的人、猪Ⅱ型胶原包板 ,采用改良的酶联免疫吸附法 (ELISA)测定 1 0 5例RA患者血清抗人、猪Ⅱ型胶原抗体IgG及IgA ,并与正常人 ( 1 4 0例 )及疾病对照组 ( 80例 )比较分析。同时检测患者的类风湿因子(RF)、血沉 (ESR)及C反应蛋白 (CRP)。结果 :RA患者血清中抗人Ⅱ型胶原抗体IgG、IgA阳性率分别为2 5 .3%、2 7.5 % ,抗猪Ⅱ型胶原抗体IgG、IgA阳性率分别为 2 6.9%、2 5 .6% ,显著高于正常人及疾病对照组 (P<0 .0 5 )。两种属Ⅱ型胶原抗体IgG及IgA常同时存在于同一患者中。两种属Ⅱ型胶原抗体与RF、ESR及CRP异常无相关性。结论 :RA患者血清中人及猪Ⅱ型胶原抗体水平升高 ,可能在RA的发病中起着一定的作用 ;但RA患者Ⅱ型胶原抗体阳性与疾病活动指标无明显相关 ,不能作为监测RA活动的指标。     

不同人群抗SARS冠状病毒特异性抗体血清学检测与分析

目的 :探索不同人群中抗SARS冠状病毒特异性抗体的发生、发展及分布规律 ;评价间接ELISA方法检测SARS冠状病毒IgG、IgM特异性抗体试剂盒及改进方法。 方法 :分别获取SARS流行前无偿献血者标本 3990份 ,一线抗SARS医务人员标本 397份和临床确诊的SARS患者标本 15 7份 ,采用ELISA方法进行SARS冠状病毒特异性抗体检测。结果 :SARS流行前无偿献血者标本 3990份共检出IgG抗体阳性标本 16份 ,阳性率为 0 .4 0 % ;IgM抗体阳性标本 0份 ,阳性率为 0 %。一线抗SARS医务人员标本 397份 ,共检出IgG抗体阳性标本 2份 ,阳性率为 0 .5 0 % ;IgM抗体均为阴性。临床确诊的SARS患者标本 15 7份 ,共检出IgG抗体阳性标本 119份 ,阳性率为 75 .79% ;IgM阳性标本 6 8份 ,阳性率为 4 3.31%。结论 :一线抗SARS医务人员与SARS流行前无偿献血者IgG、IgM抗体阳性率无显著差异 (P =0 .76 >0 .0 5 ) ;采用该SARS冠状病毒 (变异株 )IgG抗体试剂盒检测SARS流行前无偿献血者人群存在一定的阳性率 ,说明该试剂盒包被的抗原与其它免疫球蛋白 (IgG)有交叉反应 ,有待进一步改进     

抗人类白细胞抗原Ⅰ类、Ⅱ类IgG抗体在同种带瓣大动脉移植后的免疫表达

目的:探讨先天性心脏病患者移植液氮保存同种异体带瓣大动脉(CVH)后抗人类白细胞抗原(HLA)Ⅰ类、Ⅱ类IgG抗体的免疫表达规律。方法:选择2001年10月至2003年10月施行液氮保存的CVH移植术的20例复杂先心病患者,分别于术前、术后1个月、3个月、1年不同时间点,以莱姆德抗原板通过酶联免疫吸附方法检测患者血清内的抗HLA-Ⅰ类、Ⅱ类IgG抗体,并与同期施行其他复杂先心病矫正术的20例患者进行比较。结果:所有患者术前抗体为阴性,CVH移植患者在术后1个月、3个月和1年时抗HLA-Ⅰ类抗体阳性率分别为(9.28±6.64)%、(62.14±11.95)%和(66.79±13.42)%,Ⅱ类抗体阳性率分别为(22.92±15.74)%、(41.67±18.73)%、(52.92±20.01)%,且1年内两类抗体的阳性率均呈上升趋势,对照组患者则全为阴性;两类抗体表达阳性率与患者年龄呈负相关。结论:液氮保存的CVH移植后可诱导受体产生抗HLA-Ⅰ类、Ⅱ类IgG抗体介导的体液免疫反应,而且患者年龄越小这种反应越强烈。     

自身抗体与复发性流产的关系

目的 :探讨自身抗体与复发性流产的关系。方法 :采用酶联免疫吸附法 (ELISA)对 30例不明原因的复发性流产 (URSA)患者进行抗心磷脂抗体 (ACA)和抗血小板抗体 (PA)的检测 ,并与正常人进行比较。结果 :URSA组ACA～IgG、ACA～IgM或和PA～IgG的阳性率分别为 4 3.33%、30 .0 0 %和36 .6 7% ,与正常对照组相比有显著性差异。结论 :这些自身抗体的出现可能与流产有关。     

肾移植术后新生HLA抗体和MICA抗体对移植肾功能的损伤作用

目的研究肾移植术后新生人类白细胞抗原(HLA) 抗体及主要组织相容性I类相关链A抗原（MICA）抗体的产生对移植肾功能的损伤作用。方法采用免疫磁珠流式细胞仪液相芯片技术检测96例肾移植患者HLA及MICA抗体。根据检测结果,将患者分为HLA抗体阳性组（HLA+）、MICA抗体阳性组（MICA+）、以及HLA、MICA抗体阴性组（HLA /MICA ）,观察并比较各组不良免疫事件的发生率。再根据有无急性排斥（AR）,将患者分为排斥组（AR+）和非排斥（AR ）组,观察HLA抗体、MICA抗体对移植肾功能的影响。结果HLA+组急性排 斥反应发生率高于HLA /MICA 组(43．5％ vs 11.7％,P＜0.05);MICA+组急性排斥反应发生率与HLA /MICA 组比较差异无统计学意义(15．3％ vs 11．7％,P＞0．05);AR+组中,HLA+患者术后1、3、6和12个月时血清肌酐水平高于HLA /MICA 患者, MICA+患者在术后1、3月时血肌酐水平高于抗体阴性患者;AR 组中,HLA+患者术后6、12个月血肌酐水平高于HLA /MICA 患者;MICA+组在术后6个月及12个月的尿蛋白定量均值高于150?mg,并随时间逐渐升高。结论HLA抗体对移植肾功能的损伤作用表现为血清肌酐的升高以及与急性排斥反应的发生有关;MICA抗体对移植肾功能的损伤主要表现为尿蛋白定量的升高。     

不孕不育患者血清中抗精子抗体与抗心磷脂抗体的测定

目的 探讨抗精子抗体(AsAb)、抗心磷脂抗体(ACA)在不孕不育患者中的临床检测意义.方法 采用酶联免疫吸附(ELISA)法检测血清中的ACA和AsAb.1756例不孕不育患者检测了血清ACA,其中1326例不孕不育患者与20对正常生育夫妇同时检测了ACA和AsAb,1127例反复自发性流产患者(流产≥2次)(高危组)检测了ACA.结果 不孕不育组AsAb的总阳性率为21.4%,IgM阳性率为13.5%;正常生育组AsAb总阳性率为7.5%,IgM为0(均P<0.05).不孕不育组ACA检测总阳性率为36.6%,其中IgA阳性率为5.1%,IgG阳性率为30.5%,IgM为12.3%;高危组ACA阳性者471例,阳性率为41.8%,其中IgA阳性73例,占6.5%,IgG阳性398例,占35.3%,IgM阳性154例,占13.7%;正常生育组阳性率为5.0%,其中IgG阳性率为5.0%,IgM为2.5%(均P<0.05).结论 AsAb、ACA与不孕不育关系密切,其检测有助于免疫性不孕不育症的诊断.     

Serum major-histocompatibility-complex class Ⅰ-related chain A antibody detection for the evaluation of graft dysfunction in renal allograft recipients

Background In addition to the well-known antibodies against human leukocyte antigens (HLA)-induced kidney-graft rejection, polymorphic major-histocompatibility-complex (MHC) class Ⅰ-related chain A (MICA) antigens can elicit antibodies and have been suggested to play a role in the antibody-mediated allograft rejection (AMR). We carded out a prospective study of MICA antibodies in post-renal transplant patients to determine the association between MICA antibodies, C4d staining, histological features, and graft outcome.Methods We tested 52 patients who had biopsy results due to graft dysfunction. The MICA antibodies in concurrent sera were determined by Luminex. All patients were followed up for one year after renal biopsy. The influence of antibody production on the function of graft was analyzed.Results Antibodies against MICA were positive in 15 out of the 52 patients (28.9%). The presence of MICA antibodies was associated with renal-allograft deterioration. During one-year follow-up, the estimated glomerular filtration rate (eGFR) decreased (24.0±3.4)% among recipients with anti-MICA antibodies. However, among recipients without anti-MICA antibodies, the eGFR has declined only (8.4+3.0)% (P=0.017). The association between C4d staining,histological features and MICA antibody production was found no significant difference.Conclusion Besides anti-HLA antibodies, the presence of post-transplant MICA antibody is associated with poor graft outcome and increases the risk of graft failure.     

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.

     

Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma

Background  Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4⁺ T cells subsets might play a role in asthma. We investigated the relative abundance and activities of Th1, Th2, Th17 and CD4⁺CD25⁺ Treg cells in patients with allergic asthma.

Methods  Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. Plasma total IgE, pulmonary function and Asthma Control Questionnaire were assessed. The proportions of peripheral blood Th1, Th2, Th17 and CD4⁺CD25⁺ Treg cells were determined by flow cytometry. The expression of cytokines in plasma and in the culture supernatant of peripheral blood mononuclear cells was determined by enzyme linked, immunosorbent assay.

Results  The frequency of blood Th2 cells and IL-4 levels in plasma and culture supernatant of peripheral blood mononuclear cells were increased in all patients with allergic asthma. The frequency of Th17 cells and the plasma and culture supernatant levels of IL-17 were increased, whereas the frequency of CD4⁺CD25⁺ Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. Dermatophagoides pteronyssinus specific IgE levels were positively correlated with the percentage of blood Th2 cells and plasma IL-4 levels. Forced expiratory volume in the first second was negatively correlated with the frequency of Th17 cells and plasma IL-17 levels, and positively correlated with the frequency of Treg cells. However, mean Asthma Control Questionnaire scores were positively correlated with the frequency of Th17 cells and plasma IL-17 levels, and negatively correlated with the frequency of Treg cells.

Conclusions  Imbalances in Th1/Th2 and Th17/Treg were found in patients with allergic asthma. Furthermore, elevated Th17 cell responses, the absence of Tregs and an imbalance in Th17/Treg levels were associated with moderate to severe asthma. 

     

Serum major-histocompatibility-complex class I-related chain A antibody detection for the evaluation of graft dysfunction in renal allograft recipients

Background  In addition to the well-known antibodies against human leukocyte antigens (HLA)-induced kidney-graft rejection, polymorphic major-histocompatibility-complex (MHC) class I-related chain A (MICA) antigens can elicit antibodies and have been suggested to play a role in the antibody-mediated allograft rejection (AMR). We carried out a prospective study of MICA antibodies in post-renal transplant patients to determine the association between MICA antibodies, C4d staining, histological features, and graft outcome.

Methods  We tested 52 patients who had biopsy results due to graft dysfunction. The MICA antibodies in concurrent sera were determined by Luminex. All patients were followed up for one year after renal biopsy. The influence of antibody production on the function of graft was analyzed.

Results  Antibodies against MICA were positive in 15 out of the 52 patients (28.9%). The presence of MICA antibodies was associated with renal-allograft deterioration. During one-year follow-up, the estimated glomerular filtration rate (eGFR) decreased (24.0±3.4)% among recipients with anti-MICA antibodies. However, among recipients without anti-MICA antibodies, the eGFR has declined only (8.4±3.0)% (P=0.017). The association between C4d staining, histological features and MICA antibody production was found no significant difference.

Conclusion  Besides anti-HLA antibodies, the presence of post-transplant MICA antibody is associated with poor graft outcome and increases the risk of graft failure.

     

MICA抗体监测在肾移植术后急、慢性排斥反应中的意义

目的探讨肾移植受者的抗MICA抗体水平与急性和慢性排斥反应的相关性及其对移植肾功能的影响。方法采用酶联
免疫吸附方法检测接受同种异体肾移植手术的患者血清中MICA 抗体,并同步检测HLA抗体、肾功血肌酐、尿量及移植肾超声
等临床指标。本研究分两部分分别监测在肾移植术后急、慢性排斥反应中MICA抗体的变化。结果第一部分41例研究对象
中有18例发生急性排斥反应,该组中MICA抗体阳性率高于肾功能稳定组（P<0.05）;MICA抗体阳性组的急性排斥反应发生率
高于MICA抗体阴性组（P<0.05）;术后MICA抗体动态监测时发现,MICA抗体水平逐渐升高2~3 d后出现排斥反应,给予抗排
斥治疗后血肌酐水平逐渐降至正常,MICA抗体水平亦逐渐下降,但仍维持在阳性范围。第二部分40例患者中21例患者出现
慢性排斥反应,其中MICA抗体阳性率明显高于肾功稳定组患者（P<0.05）。慢排组中MICA抗体阳性患者的血肌酐与阴性组
的血肌酐水平比较有统计学差异（P<0.05）。移植肾穿刺病理结果显示MICA抗体阳性患者C4d沉积均为阳性。结论MICA
抗体可预测急性排斥反应的发生及治疗效果,对于及时诊断及治疗排斥反应提供了一个重要指标,同时也是导致慢性排斥的主
要因素之一,可影响移植肾的长期存活。
     

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.

     

肾骨髓联合移植与嵌合体发生及急性排斥反应的关系

目的　研究肾骨髓联合移植与嵌合体发生及急性排斥反应的关系。方法　采用供体骨髓与肾脏联合移植 ,进行 2 4例造血干细胞微嵌合体诱导 ,采用聚合酶链反应 (PCR)技术检测受者嵌合状态 ,与单纯肾脏移植组 37例比较嵌合发生率及急性排斥反应发生率。结果　随访 1年 ,肾骨髓联合移植组术后嵌合体发生率 (87 5 % ,2 1/ 2 4 )明显高于单纯肾脏移植组 (40 5 % ,15 / 37) ,差异有显著意义 (P 0 0 0 1) ;嵌合阳性组急性排斥反应发性率 (19 4 % ,7/ 36 )与嵌合阴性组 (44 % ,11/ 2 5 )相比差异有显著意义 (P <0 0 5 )。结论　肾骨髓联合移植可诱导嵌合体发生并增加受者对供体器官的免疫耐受 ,降低急性排斥反应发生率 ,嵌合现象与免疫耐受具有相关性     

肾移植术后长期应用环孢素2332例的临床远期随访?

目的：总结肾移植术后长期应用环孢素( CsA)的临床经验。方法分析接受首次肾移植、术后长期服用CsA 并维持随访的受者2332例。根据患者的年龄分为儿童组(<18岁)27例,成人组(18~60岁)2086例,高龄组(>60岁)219例,计算所有患者及分组的排斥反应发生率和1、3、5、10年人、肾存活率,并以成人组为对照,分别与儿童组、高龄组进行上述指标的比较。统计长期服用CsA不良反应的发生率。结果所有患者、儿童组、成人组以及高龄组急性排斥反应( AR)发生率分别为17．0%、40．7%、17．1%、13．2%,慢性排斥反应( CR)发生率相应为13．2%、29．6%、13．4%、9．1%;1、3、5、10年人、肾存活率分别为：所有患者97．0%/96．7%、93．2%/86．2%、88．4%/82．7%、83．4%/65．4%,儿童组96．3%/96．3%、92．6%/85．2%、88．9%/81．5%、81．5%/63．0%,成人组97．5%/96．9%、93．4%/86．1%、88．9%/82．8%、84．0%/65．3%以及高龄组94．5%/94．1%、91．8%/87．2%、83．6%/82．2%、78．1%/66．2%。儿童组AR、CR发生率高于成人组(P=0．003, P=0．022),但人/肾存活率与成人组比较差异无统计学意义(P=0．34, P=0．08)。高龄受者CR发生率低于成人组(P=0．035),生存率低于成人组(P=0．009),AR和移植肾存活率与成人组类似(P=0．074, P=0．28)。 CsA的不良反应有：肝功能损害(16．5%)、肾中毒(17．7%)、高脂血症(17．4%)、高血压(32．8%)、糖代谢异常(13．2%)、牙龈增生(35．7%)以及多毛(24．1%)等。通过减少 CsA剂量、免疫抑制剂联合用药、对症治疗等措施,多数患者症状消失或缓解。结论 CsA是一种安全、有效的免疫抑制剂,除可用于成人肾移植之外还可用于儿童及高龄受者。移植术前良好的HLA配型,CsA精准浓度调控以及联合用药有利于降低CsA剂量,从而减少CsA不良反应的发生。     

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.