再次免疫应答导致肾移植后早期严重急性体液排斥反应

背景：国内外有关预防高致敏受者肾移植后发生超急性、急性排斥反应提高人肾存活率取得满意效果,然而临床对群体反应性抗体检测阴性既往致敏受者肾移植后发生再次免疫应答研究则罕见报道。 目的：探讨群体反应性抗体阴性的既往致敏受者肾移植后早期发生严重急性体液性排斥反应机制,为其早期诊断和治疗既提供参考依据。 方法：选择21例群体反应性抗体阴性术后早期发生严重急性体液性排斥的首次肾移植患者,动态分析移植后14 d内反映急性体液性排斥的相关指标,包括IgG型抗HLA抗体,病理苏木精-伊红染色、C4d及细胞表面分子原位检测。 结果与结论：21例患者既往均有输血或妊娠史;18例患者移植后第7天抗HLAⅠ类IgG抗体阳性率>80%,11例于移植后第7天抗HLA Ⅱ类IgG抗体> 80%;5例女性患者于移植后第5~8天发生移植肾破裂,抗HLAⅠ类和Ⅱ类IgG抗体均>96%;21例受者均检出抗供者特异性抗体(DSA),13例(61.90%)供、受者存在HLA-A2和HLA-A11的错配并产生对应DSA,包括5例移植肾破裂受者;病理组织形态学均有不同程度急性损伤,免疫组化可见管周毛细血管区(PTC)C4d沉积,原位染色CD34(+)、CD68(+)、CD4(+)。提示移植前群体反应性抗体监测不能完全反映受者的预致敏状态;移植后早期监测群体反应性抗体可预测和诊断既往致敏受者急性体液性排斥的发生;C4d、CD68(+)作为其的辅助诊断指标,可提高诊出率;HLA-A2和HLA-A11在既往致敏受者是高危致敏基因。     

应用流式补体依赖淋巴细胞毒技术检测肾移植病人HLA抗体

目的为了更好地识别造成移植肾排斥的特异性抗供者HLA的IgG类型同种抗体，对Flow-CDC方法应用于肾移植及其临床相关性进行研究。方法对96例等候肾移植受者同时进行PRA、NIH-CDC和FloW-CDC实验，并观察其中34例接受NIH-CDC阴性肾移植术的受者近期移植效果。结果FloW-CDC和NIH-CDC两种实验方法的阳性率[27．8％（42／151）和17．3％（26／151）]之间差异有统计学意义（X^2=4．86，P〈0．05）。另外，PRA阴性受者其NIH-CDC和Flow-CDC均为阴性，阴性吻合率为100％；在接受同种异体肾移植术的34例受者，其中20例PRA阴性受者接受了NIH-CDC和Flow-CDC均阴性供肾，移植后未发生排斥，移植肾功能迅速恢复；13例PRA阳性的致敏受者接受NIH-CDC和Flow-CDC均阴性供肾的，1例发生急性排斥经治疗后逆转，12例无排斥移植肾功能良好；1例PaA阳性再次移植受者接受了NIH-CDC阴性而Flow-CDC阳性的供肾，移植后第2天出现少尿，10d切除移植肾。结论Flow-CDC方法是一种能够识别具有补体结合能力的抗供者特异性HLA抗体的交叉配型技术，比经典的NIH-CDC方法具有更敏感、可标准化、快速等优点，对预示肾移植术后的排斥反应方面更具有前瞻性。     

肾移植群体反应性抗体的检测及其临床应用

目的 :探讨人类白细胞抗原 (HLA)群体反应性抗体 (PRA)对肾移植效果的影响。方法 :采用酶联免疫吸附法 (ELISA)对 2 0 6例肾移植受者的血清PRA进行检测。同时对 14 0份血清分成四组包括首次移植术前及术后 1个月 ,半年至 1年肾功能稳定期病人 ,第一次尸肾移植失功恢复血透病人进行PRA检测。结果 :PRA阴性组受者移植术后排斥发生率为 11 85 % ,阳性组受者平均PRA高达 4 6 5 % ,两组比较差异显著 (P <0 0 0 1)。首次移植术前A组PRA阳性率 17 1% ,术后B组PRA阳性率 31 4 % ,肾功能稳定组 (C组 )PRA阳性率 14 3%。而移植失功恢复血透者 (D组 )PRA阳性率达 77 1%。结论 :PRA的检测是肾脏移植术前筛选致敏受者的重要指标 ,对肾脏移植后排斥反应和移植物存活率关系密切。     

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     

HLA抗体筛选技术的最新进展及其在器官移植中的应用

人类白细胞抗原(HLA)是介导器官移植排斥反应的主要因素,良好的组织配型是肾移植患者长期存活和术后移植肾功能恢复的重要条件之一。在多次输血、生育史、再次移植的受者受到同种HLA免疫致敏可产生群体反应性抗体(panelreactive antibody,PRA)。PRA是一组特定的人类白细胞抗原(HLA)抗体,有多种类型,包括HLA-A、B、C、DR、DQ等抗体[1],是造成超急性和加速性排斥反应和移植物丢失的危险因素之一。PRA水平的高低更直接地影响移植肾的近期存活率。因此,将抗体筛选技术应用于器官移植实践,对减少移植后排斥反应,提高移植成功率和移植…     

HLA配型、群体反应性抗体与肾移植术后早期急性排斥反应的关系

目的：研究人类白细胞抗原(HLA)配型、群体反应性抗体(PRA)与肾移植术后早期急性排斥反应的关系。方法：应用单克隆抗体板、微量序列特异性引物、混合抗原板进行供受者HLA-I类抗原分型、HLA-Ⅱ类基因分型、PRA检测。结果：PRA为低、中、高三组受者的早期急性排斥反应发生率分别为16％、27％、66．6％。HLA位点错配数(MM)为0-1组明显比5—6组早期急性排斥反应率低。结论：良好的组织配型、低水平的PRA，可降低早期急性排斥反应的发生。     

高PRA介导肾移植后延迟性超急排斥反应

目的：了解HLA-A、B、DR、DQ表现型为纯合子的终末期肾脏疾病患者的PRA水平,并研究其与肾移植预后的关系。方法：对2006年8月至2007年8月间在我院登记等待首次肾移植的438例终末期肾脏疾病患者HLA、PRA情况以及其中1例PRA65的HLA纯合子患者肾移植效果进行分析。HLA基因分型采用PCR-SSP技术,PRA、抗体强度及抗体特异性分析采用ELISA技术,数据统计采用SPSS11.5统计软件。结果：438例患者中有HLA纯合子12例,杂合子426例;12例纯合子中PRA阳性者6例,阳性率50,平均HLA抗体强度为55,广泛致敏率达100;426例杂合子中PRA阳性者65例,阳性率15.26,平均HLA抗体强度为28,广泛致敏率为40;纯合子与杂合子之间的PRA阳性率、平均HLA抗体强度和广泛致敏率相比差异均有统计学意义（P〈0.05）,纯合子高PRA的风险大（OR=5.29,95CI：1.67～16.70）;1例PRA65的纯合子患者术前经血浆置换、蛋白免疫吸附、静滴丙种球蛋白治疗使PRA降低至阴性,在舒莱免疫诱导下行尸体肾移植术,供受者HLA抗原2个错配,术后移植肾功能逐渐恢复,第3天开始PRA呈阳性并逐渐升高,伴随临床逐渐出现尿少、血压升高、移植肾区疼痛等排斥反应征象,血清肌酐逐渐升高,移植肾B超见动脉阻力指数逐渐升高,提示急性排斥反应,采用术前有效清除HLA抗体的所有方法再次治疗无效,于术后第36天因移植物失功行移植肾切除。结论：HLA纯合子产生高PRA的风险大;文中1例PRA阳性的HLA纯合子早期移植肾功能恢复随后出现不可逆排斥反应致移植肾失功的情况,提示近年来随着各种有效清除HLA抗体的治疗方法不断用于临床导致了抗体介导的延迟性超急排斥反应（AMDR）的出现从而使移植肾失功;高PRA患者行肾移植术需高度慎重,应尽可能避开受者PRA峰值时的全部抗体谱来选择供体。     

肾移植受者术前HLA特异性抗体筛查(附3 500例报告)

目的:预致敏的人白细胞抗原特异性抗体(HLA)是抗体介导排斥反应的主要危险因素.本研究对肾移植受者术前进行HLA特异性抗体检测和分析,以评价其致敏状态.方法:1998年至2007年于我院等待肾移植的受者共3 500名.2000年3月前694名受者采用补体依赖微量细胞毒性试验(CDC)进行群体反应性抗体(PRA)检测,之后2 806名受者改为用酶联免疫吸附实验(ELISA)检测.对致敏受者HLA抗体多样性和特异性,以及致敏相关因素进行分析.结果:CDC方法仅能检出抗HLAⅠ类IgG抗体,而ELISA可检出抗HLAⅠ类和Ⅱ类抗体.CDC方法所检出的病人血清PRA阳性率比ELISA方法检出的阳性率低.而且,ELISA能分别检出抗HLA-A、B、CW、DR和DQ抗原的抗体20种、37种、8种、14种和7种.抗HLA-A2、24、68、23、32;B27、56、57、7;DR7、4、9、13、17、12;CW1、2、6、4、8 等位基因产物的抗体频率较高.这些抗HLA抗体与华南地区人群HLA抗原分布不尽一致.不同性别PRA阳性率存在显著性差异,男性以输血致敏为主,女性以输血、妊娠致敏为主.结论:采用ELISA方法能较为准确地检出抗HLA特异性抗体.避免供受者间常见高频抗体相应的HLA位点的错配和减少输血是减少抗HLA抗体的产生,以提高移植物存活的有效手段.     

HLA配型和DSA对移植肾功能的影响研究

器官移植中良好的供受者间HLA配型对预防移植肾早期排斥和移植肾的长期存活具有重要意义.肾移植术后发生排斥的重要因素之一是群体反应性抗体(PRA)的参与,特别是肾移植术后产生抗供者特异性抗体(DSA).因此本文对肾移植供受者HLA分型和DSA对移植肾急性排斥反应和近期肾功能进行研究.现报道如下. 材料和方法 一般资料:选择了2007年10月至2009年12月间在我院接受肾移植的128例患者,男性88例,女性40例;最大年龄63岁,最小年龄20岁.     

HLA致敏性错配对肾移植受者急性排斥反应发生率的影响

目的　探讨供受者HLA致敏原性错配(IM)对肾移植受者急性排斥反应发生率的影响。方法　回顾性分析196例首次肾移植受者IM对肾移植术后肾功能恢复时间及1年内排斥反应发生率的影响。结果　IM对肾移植术后肾功能恢复时间无明显影响;IM患者1年内急性排斥反应发生率明显增加,各类位点IM对肾移植术后急性排斥的影响比较,A位点影响不大,B位点与急性排斥有关,DR位点IM可致急性排斥明显增加。结论　在临床采用HLA氨基酸残基配型标准判断组织配型的同时,IM不容忽视,HLA B位点IM与肾移植术后急性排斥反应相关,HLA DR位点IM明显影响肾移植术后急性排斥反应发生率。     

Is presensitization relevant to liver transplantation outcome?

The impact of anti-HLA antibodies and crossmatch (CM) on liver transplantation (LT) outcome is still controversial. In this retrospective study we analyzed LT outcome according to pretransplant pre-formed anti-HLA antibodies and CM status. Serum anti-HLA antibodies were screened by ELISA assay, utilizing One Lambda antigen tray-mixed (LAT-M). CMs were performed by the complement dependent cytotoxicity test using Dithiotreitol treated sera. Anti-HLA antibodies were studied in 80 recipients; 56/80 had positive LAT-M tests (PLAT-M), whereas the remaining 24 recipients tested negative for both classes I and II (NLAT-M). Rejection episodes were more frequent in PLAT-M compared with NLAT-M group in post-LT intervals of <1 week (p = 0.05), 1 week-3 months (p = 0.035), and 3-12 months (p = 0.076). Graft and patient survival rates were better, albeit not significantly, in the NLAT-M compared with PLAT-M recipients. CM status was investigated in 62/80 recipients, 18/62 recipients had positive CM (PCM), and 44 had negative CM (NCM). Five of 18 PCM recipients (28%) experienced early graft loss compared with 1/44 (2%) with NCM (p = 0.006). Rejection episodes were more frequent within first 3 months post-LT in PCM recipients compared with NCM (p = 0.015). One-year graft survival rate was better in NCM, compared with PCM recipients (graft loss of 2/44 vs 5/18). NCM PLAT-M had a higher incidence of rejection episodes compared with the NCM NLAT-M group (p = 0.031). The presence of anti-HLA antibodies suggests a deleterious effect on LT outcome, and was associated with an increased incidence of early graft loss and rejection episodes.     

Good kidney transplant outcome in recipients with presensitization against HLA class II but not HLA class I

It is a matter of debate whether pretransplant anti-human leukocyte antigen (HLA) class II antibodies contribute to the increased graft rejection rate found in presensitized recipients. We investigated the influence of preformed anti-HLA class II antibodies on graft survival in 5949 cadaver kidney transplants. Pretransplant recipient sera were tested in enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig)G-anti-HLA class I and IgG-anti-HLA class II antibodies. A total of 672 recipients with antibodies against HLA class II but not against HLA class I had a 3-year graft survival rate of 80 +/- 2%, identical to the 80 +/- 1% rate in 4561 recipients who were negative for anti-HLA class I and II (p = NS). Graft survival was significantly lower in 365 recipients who were positive for both anti-HLA class I and II (65 +/- 3%, p < 0.0001). Compatibility for HLA-A+B+DR influenced graft survival significantly in anti-HLA class I- and II-positive recipients (p = 0.0016), whereas no significant HLA effect was found in patients with antibodies directed against only class I or II. Surprisingly, not even incompatibility for HLA class II antigens of the DR locus caused a significant impairment of graft survival in anti-class II-positive recipients. We conclude that the risk associated with sensitization against HLA class II in the absence of sensitization against HLA class I is negligible.     

ELISA methods detect HLA antibodies with variable sensitivity

The accuracy of human leukocyte antigen (HLA) antibody screening results is dependent on the technique employed. In this study, a total of 612 serum samples from patients awaiting kidney transplantation were tested by two different enzyme-linked immunosorbent assay (ELISA) methods: LAT-M(R) (One Lambda/BMT) and AbScreen(R) (Biotest). The results of these assays were identical for HLA class I and II antibodies in 524 cases (85.6%), and discrepant in the remaining 88 cases (42 class I, 24 class II, 22 class I and II). More specifically, class I results were in agreement in 26 positive and 522 negative cases and in disagreement in 64 cases. Class II results were the same in 50 positive and 516 negative cases and different in 46 cases. Retesting the samples using LAT 1288 (One Lambda/BMT) and considering previous HLA antibody test results and the history of immunising events, the sensitivity and specificity, respectively, of the two methods were determined as follows: class I: 89.6% and 97.5% (LAT-M) vs. 70.6% and 96.8% (AbScreen), class II: 96.5% and 98.4% (LAT-M) vs. 88.3% and 95.5% (AbScreen). These results indicate that a single ELISA does not invariably prove or exclude the presence of HLA antibodies, and that additional testing is required in some cases.     

Vaccination against Streptococcus pneumoniae does not induce antibodies against HLA or MICA in clinically stable kidney transplant recipients

There are concerns in the community that immune activation after vaccination could lead to (subclinical) rejection. Our aim was to define if pneumococcal vaccination induced HLA antibodies using highly sensitive methods. Forty-nine kidney transplant recipients were immunized with Pneumovax 23. The median interval between transplantation and vaccination was 6.5 years, the median serum creatinine concentration 1.3, 1.3 and 1.4 mg/dL pre-vaccination, at month 1 and 15 post-vaccination, respectively. In none of the patients biopsy-proven acute rejection was diagnosed within three years post-vaccination. Pneumococcal, HLA class I and II and major histocompatibility class I-related chain A (MICA) antibodies were determined by Luminex™ technology (xMAP™ Pneumococcal Immunity Panel and LABScreen™ Mixed beads, respectively) and HLA antibodies also by ELISA (Lambda Antigen Tray™). While pneumococcal antibodies were significantly higher at month 1 and 15 post- vs. pre-vaccination (p < 0.0001 each), HLA/MICA antibodies remained unchanged as determined by Luminex™ and ELISA. Positive Luminex™ reactions were present in 63%, 67% and 63% (HLA class I), 47%, 47% and 55% (HLA class II) and 29%, 29% and 29% (MICA) pre-vaccination, at month 1 and 15, respectively. In clinically stable kidney transplant recipients there is no evidence for an increase in HLA antibodies after pneumococcal vaccination.     

Association of kidney transplant failure and antibodies against MICA

Despite the progress in renal transplantation, acute rejection and graft failure still occur and chronic rejection continues to be the main problem in long-term allograft survival. Although kidney transplant rejection has been linked to anti-HLA antibodies, not all patients with failed kidney transplants have anti-HLA antibodies, indicating that other loci may be involved. Sera of 63 patients who experienced kidney rejection were compared against sera of 82 patients with functioning transplants. Sera were examined for IgG and IgM anti-HLA Class I and II antibodies. They were also tested by cytotoxicity against panels of 26 endothelial cell lines, 8 MHC class I chain-related gene A (MICA) recombinant cell lines, and 28 B lymphoblast cell lines. Among patients whose transplants failed, 65% had anti-HLA antibodies compared with 45% of those with functioning kidneys (p < 0.05). Similarly, among those whose transplants failed, 41% had anti-endothelial cell antibodies in contrast to 22% in functioning patients (p < 0.05). Among patients whose grafts failed, 52% had anti-MICA antibodies versus 21% of those with functioning grafts (p < 0.001). Eleven patients with failed grafts and 32 with functioning grafts were negative for all of the above. However, 6 of the former and 7 of the latter showed positive cytotoxicity against B lymphoblasts (p < 0.05). Taking all antibodies together, 92% of patients with graft failure had antibodies as opposed to 70% of patients with functioning grafts (p < 0.001). We postulate that antibodies against HLA, MICA, endothelial cells, and B lymphoblasts could be independently involved in the slow process of chronic graft failure.     

Post transplant development of MICA and anti-HLA antibodies is associated with acute rejection episodes and renal allograft loss

This study was undertaken with the primary aim of analyzing the clinical relevance of posttransplant appearance of anti-human leukocyte antigen (HLA) and major histocompatibility (MHC) class I related chain A (MICA) antibodies in response to live related donor (LRD) renal transplantation. A total of 185 consecutive post renal transplant recipient serum samples were analyzed for the detection of anti-HLA by enzyme-linked immunoabsorbent assay (ELISA) and MICA antibodies using Luminex techniques. Patients with IgG HLA class I antibodies had more acute rejection episodes compared to the negative group (67% vs. 20%, chi(2) = 7.95, p = 0.005) and also had poor graft survival (44% vs 86%, chi(2) = 6.67, p = 0.01). Similarly, patients with anti-HLA class II antibodies also had significantly lower graft survival and a higher number of rejection episodes as compared to the antibody negative group (p = 0.002 and p = 0.000, respectively). Following transplantation, 30 patients (16%) developed antibodies against any of the MICA alleles (MICA*001, MICA*002, MICA*004, MICA*008, or MIC*009). The graft survival was significantly compromised in these patients as compared to the negative group (60% vs 86%, chi(2) = 10.26, p = 0.001). Further, patients carrying both antibodies (MICA+/HLA+) were the worst affected and showed significantly poor graft survival as compared to the MICA-/HLA- group (17% vs 89%, chi(2) = 19.63, p = 0.000). Similarly, patients with only MICA antibodies or those with only HLA antibodies also had significantly lower graft survival and a higher number of acute rejection episodes (p = 0.035 and p = 0.001, respectively) as compared to the nonsensitized group. The study illustrates that posttransplant monitoring of antibodies to both MICA as well as HLA could be an important prognostic marker in renal transplant subjects.     

Effect of antiidiotypic antibodies to HLA on graft survival in renal-allograft recipients

Although the presence in the recipient of preformed antibodies to HLA antigens in the kidney of a renal-transplant donor may be associated with early graft failure, such grafts are often well tolerated. We have investigated the possibility that anti-anti-HLA (antiidiotypic) antibodies influence the outcome of renal transplantation in recipients with a history of presensitization to their donor's HLA antigens. A retrospective analysis of 20 such cases showed that in 10 patients the transplanted kidney was rejected within one month, whereas in the remaining 10 the graft was tolerated for more than a year. Nine of the 10 patients in whom the graft was tolerated had anti-anti-HLA antibodies at the time of transplantation. Nine of the 10 patients in whom the graft was rejected had antibodies that potentiated, rather than blocked, the cytotoxic activity of anti-donor-HLA antibodies. These results suggest that patients with anti-anti-HLA antibodies specific for a potential donor can safely undergo transplantation, despite a prior history of anti-HLA antibodies. At the time of transplantation, patients who have antibodies that potentiate the cytotoxic activity of a historically positive serum are at high risk of graft rejection within a short period. Taking these considerations into account may improve the reliability of cross-matching in renal transplantation.     

Anti-HLA class II antibodies in kidney retransplant patients

The relevance of anti-HLA class II antibodies for kidney graft survival is still controversial. In part, this can be attributed to difficulties to detect and differentiate anti-HLA class II antibodies. Anti-HLA class II IgG antibody screening was performed by enzyme-linked immunosorbent assay. Subsequently, all anti-HLA class II-positive sera were subjected to the determination and specification using color-coded microspheres coated with purified HLA antigens. In a cohort of 934 patients awaiting kidney transplantation, 41 sera (4.4%) were positive for IgG anti-HLA class II antibodies. The presence was confirmed in 90.2% sera by retesting. Subsequently, all anti-HLA class II-positive patients (n = 27) who in the past had undergone a kidney transplantation with an HLA-DR and/or -DQ-mismatched graft were selected. In 25 of 27 sera (92.6%), the alloantibody specificities corresponded to the known previous transplant mismatches on a broad antigen level. In 20 of 27 sera (74.1%), anticlass I antibodies were detected as well. Anti-HLA-DP antibodies were seen in 24 of the 27 sera of this cohort. In the majority of the cases, the reactivities with different DPB1 alleles could be explained by involvement of a single, specific DPB1 epitope. Donor-specific anti-HLA-DR and -DQ antibodies were seen in the majority of cases with graft failure following HLA class II alloantigen exposure in prior kidney transplantations. In addition, HLA-DP may serve as a transplantation antigen in kidney transplantation, leading to a humoral response.     

Major histocompatibility complex class I-related chain A allele mismatching, antibodies, and rejection in renal transplantation

Even when kidney allografts are well matched for human leukocyte antigen (HLA) and anti-HLA antibodies are not detected, graft rejection can still occur. There is evidence that some patients who lose their graft have antibodies specific for major histocompatibility complex (MHC) class I-related chain A (MICA) antigens. We investigated whether mismatching MICA alleles associates with MICA antibody production and graft rejection or dysfunction. MICA and HLA antibody screening in 442 recipients was performed, and specificities were confirmed in a subgroup of 227 recipients using single-antigen multiplex technology. For assignment of MICA antibody specificity, we used three independent assays. In addition, MICA alleles of 227 recipients and donors were determined by DNA sequencing. In all, 17 patients (7.5%) had MICA antibodies, and 13 patients (6%) developed MICA donor-specific antibodies (DSA). Multivariate analysis revealed MICA mismatching, as an independent significant factor associated with the presence of MICA antibodies (p = 0.009), and 14 mismatched MICA residues significantly correlated with MICA antibody production. MICA and HLA antibodies significantly associated with acute rejection (AR) and MICA DSA and HLA DSA correlated with decreased graft function by univariate and multivariate analysis. We conclude that mismatching for MICA epitopes in renal transplantation is a mechanism leading to production of MICA antibodies that associate with AR and graft dysfunction.