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1、高群体反应性抗体的血液净化Purification In Highly Sensitized Renal Transplant Recipients,器官移植中心血透室 The Dialysis Center，Hunan Organ Transplantation Academy,目前常用的组织配型方法 Main tissue matching methods,1. ABO血型:血型基因型只有6种基因而随机人群中容易获得配合. 2. CDC试验:检测患者体内针对供者特定位点的抗体. 3.PRA检测:检测患者体内针对同种HLA抗原的抗体. 4.HLA配型:理想的配型,尤其位点相配可使存活率提高1
2、0%30%,对再次移植和高危患者效果更明显，具有10亿个基因型高度多态性的成为选择配合移植的主要难题。 Main tissue matching methods include ABO blood type crossmatch, CDC (complement-dependent-cytotoxicity) test, PRA(panel reactive antibody) detection and HLA (human leukocyte antigen)typing. HLA-A,B,DR locus especially DR locus well matched will imp
3、rove the survival rate for 10-30% while it is very difficult to do so in practice.,的检测原理 The principle of PRA test,利用已知抗原的淋巴细胞与未知血清及补体孵育,如患者血清中含有与淋巴细胞表面特异结合的抗体,在补体存在的情况下,可发生细胞溶解作用,根据细胞溶解程度判断患者的免疫状态及HLA抗体的特异性。 The principle of PRA test is that the lymphocytes whose antigens were known were incubated
4、with complements and patients sera together, then we can judge these patients immune status and the specificity of HLA antibodies according to the degree of cytolysis.,检测的意义 (The sense for PRA test）,反映受者人类白细胞抗原体液致敏状态,增高，移植后导致急性、超急性、加速排斥反应和肾功能延迟，移植前水平的峰值比在手术时检测更能预测移植物存活的结果。高受者的抗体为性质,或曾经出现高峰值,近期自然或人为干
5、预下降,其诱导排斥反应的作用仍然存在,术后超急、加速排斥率均比阴性高80%。 The test result of PRA can affect recipient sensitivity status of humoral immunity. It was proved that high PRA pretransplantation can lead to episodes of acute, hyperacute, accelerated rejection of renal allografts or delayed renal graft function.,的产生原因 Why di
6、d the PRAs produce?,抗体产生绝大多数由移植前输血、妊娠和再次移植所致,极少数可能是由某些病毒或细菌的分解物所携有的类似抗原所致。初次移植病人阳性率有明显性别差异,男女=836. 6,有两种或多重致敏经历的病人通常峰值高居不降。 Preformed circulating cytotoxic IgG anti-HLA alloantibodies induced by previous failed grafts, blood transfusion, pregnancy or infection are a relative contraindication to allo
7、transplantation and apt to result in hyperacute rejection. 其他因素:(1)受者 A1或 2表型者易致敏;(2)黑人受者普遍高,且接受黑人移植物比接受白人或黄种人移植物的排斥率高;(3)长时间的血液透析。 (1) CDC test revealed that A1 and A2 antigens were highly immunogenic;（2）The black race commonly has high PRA；（3）Undergoing the hemodialysis for long time.,的分类 Classify
8、 the PRA,高所针对的免疫原可以是抗原,也可以是非成份,抗HLA 类抗原的抗体,包括IgG14、IgM和IgA,引起超急性排斥反应的主要是IgG1类抗体, IgG1对术后第1年发生排斥反应的预测值为77.5%,而IgG24及IgM的预测值为0。IgA的有益作用机制可能为阻断IgG及补体介导。 PRA mainly aim directly at HLA which comprise IgG14、IgM and IgA. Only IgG1 antibodies account for hyperacute and accelerated rejection. IgG24 and IgM
9、class antibodies are not associated with posttransplant rejection. furthermore, IgA does good to rejection reaction by its blockage to complements and IgG .,PRA的分度 Grading of PRA,据PRA值可将患者分为非致敏性(30%)。 According to the test value, patients with elevated PRA can be divided into nonsensitized patients
10、(30%).,超急性排斥反应的其它因素 Other factors account for hyperacute rejection,超急性排斥反应的发生除与体内预存抗HLA抗原的细胞毒抗体有关外,尚有其他引发因素,如冷凝集素、抗内皮细胞抗体及其他非HLA抗体。大部分研究认为,抗内皮细胞抗体可在排斥反应中起作用,并证明其与单核细胞及角化细胞反应,不与淋巴细胞反应。这种抗体可逃避交叉配型的检测。 Hyperacute rejection is mainly induced by preformed antibodies to HLA while other antibodies such as
11、those antibodies to endothelial cells which are proved to interact with mononuclear cells as well as keratinocyte, not lymphocyte. Those antibodies can not be tested by common crossmatch.,高群体反应性抗体的预防 Prevention strategy for highly PRA,1.避免随机输血;使用促红素代替输血; 2.对供者的进行监测； 3.对受者水平动态监测,准确了解其致敏状态,正确判断其致敏抗体的特
12、异性; 4.术前注重配型; 5.选择降低时移植或等待自然消退时行移植手术 。 1. Avoid random blood transfusion and apply for erythropoietin(EPO) instead of blood transfusion. 2. Long-term monitor the levels of donor PRA. 3. Long-term monitor the levels of recipient PRA so as to supervise recipient sensitivity status of humoral immunity.
13、 4. One approach to reduce the formation of high PRAs is to diminish such cross-reactivity by avoiding certain mismatches. 5. Select the proper time when PRAs decrease to a low level to develop kidney transplantation.,高群体反应性抗体的处理 Treatment of patients with high PRA,1.药物抑制：包括环磷酰胺、6-巯基嘌呤、骁悉(cellcept)等
14、; 2.免疫诱导； 3.静脉注射免疫球蛋白(IVIG); 4.血浆置换; 5.免疫吸附; 1. Depress the production of PRA by applying for some drugs such as cyclophosphamide(), mercaptopurine(6 -), mycophenolate mofetil (MMF) and so on. 2. Induce to immune toleration. 3. Applying for intravenous immunoglobulin (IVIg). 4. Therapeutic plasma ex
15、change. 5. Therapeutic immunoadsorption.,免疫诱导 Induce to immune toleration,小剂量ATG、OKT3诱导治疗，ATG可以降低PRA值,在治疗加速性及急性排斥方面很有成效。但是它也有使白细胞、血小板下降,增加细菌、病毒感染,-球蛋白增高及肿瘤发生率升高等问题，也有报道认为,术前应用ATG、OKT3等诱导疗法并未减少术后6个月内的排斥反应发生次数。 Little dose of ATG( antithymocyte globulin)or OKT3 can reduce PRA levels so they can treat
16、accelerated and acute rejection successfully. Unfortunately they may lead to the side effects of reducing leukocyte and platelet and lead to infections. Furthermore some research showed the using of ATG or OKT3 did not lower the frequency of rejection within the first 6 months posttransplantation.,免疫球蛋白降高PRA Depress PRA by using immunoglobulin,免疫球蛋白主要通过拮抗自身的抗独特型抗体及阻断抗原结合部位而发挥降作用,浓度越高,拮
