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准备接受首次移植的终末期肾病患者的 HLA 表型与抗 HLA 抗体状态的关联。

Association of HLA phenotypes of end-stage renal disease patients preparing for first transplantation with anti-HLA antibody status.

机构信息

Department of Medical Biology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.

出版信息

Ren Fail. 2010 Jan;32(3):380-3. doi: 10.3109/08860221003615803.

Abstract

Patients with pre-transplantation high levels of panel reactive antibody (PRA) have an increased risk of graft failure, and renal transplantation in sensitized patients remains a highly significant challenge worldwide. The influence of anti-human leukocyte antigen (HLA) antibodies on the development of rejection episodes depends on patient-specific clinical factors and differs from patient to patient. The HLA typing of the recipient might influence the development of anti-HLA antibodies. Some HLA antigens appear to be more immunogenic than others. The aim of this study is to demonstrate the distribution of HLA phenotypes in PRA-positive and PRA-negative end-stage renal disease (ESRD) patients on the basis of having sensitizing events or not. Our study included 642 (mean age: 41.54; female/male: 310/332) ESRD patients preparing for the first transplantation and who are on the cadaveric kidney transplantation waiting list of Istanbul Medical Faculty in 2008-2009. Class I HLA-A,B typing was performed by complement-dependent cytotoxicity (CDC) method, whereas class II HLA-DRB1 typing was performed by low-resolution polymerase chain reaction (PCR)-sequence-specific primer (SSP). All serum samples were screened for the presence of IgG type of anti-HLA class I- and II-specific antibodies by enzyme-linked-immunosorbent assay (ELISA). PRA-negative group consisted of 558 (86.9%) and PRA-positive group included 84 (13.1%) patients. We have found statistically significant frequency of HLA-A3 (p=0.018), HLA-A66 (p=0.04), and HLA-B18 (p=0.006) antigens in PRA-positive patients and DRB107 (p=0.02) having the highest frequency in patients with sensitizing event history but no anti-HLA development suggesting that DRB107 might be associated with low risk of anti-HLA antibody formation.

摘要

移植前 panel reactive antibody(PRA)水平较高的患者发生移植物失功的风险增加,而致敏患者的肾移植仍然是全球范围内的一个重大挑战。抗人类白细胞抗原(HLA)抗体对排斥反应发生的影响取决于患者的具体临床因素,并且在不同患者之间存在差异。受者的 HLA 分型可能会影响抗 HLA 抗体的产生。一些 HLA 抗原似乎比其他抗原更具免疫原性。本研究旨在根据致敏事件的有无,证明 PRA 阳性和 PRA 阴性终末期肾病(ESRD)患者 HLA 表型的分布。

我们的研究纳入了 2008-2009 年在伊斯坦布尔医学院等待尸体肾移植的 642 名(平均年龄:41.54;女性/男性:310/332)准备首次移植的 ESRD 患者。采用补体依赖性细胞毒性(CDC)法进行 HLA-A、B 类Ⅰ型基因分型,采用低分辨率聚合酶链反应(PCR)-序列特异性引物(SSP)进行 HLA-DRB1 类Ⅱ型基因分型。通过酶联免疫吸附试验(ELISA)检测所有血清样本中 IgG 型抗 HLA Ⅰ类和Ⅱ类特异性抗体的存在。PRA 阴性组包括 558 例(86.9%),PRA 阳性组包括 84 例(13.1%)患者。我们发现 PRA 阳性患者 HLA-A3(p=0.018)、HLA-A66(p=0.04)和 HLA-B18(p=0.006)抗原的频率有统计学意义,具有致敏事件史但无 HLA 抗体产生的患者中 DRB107 抗原的频率最高(p=0.02),提示 DRB107 可能与低风险的抗 HLA 抗体形成有关。

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