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肾移植受者不同队列中的HLA匹配效应:10年后

The HLA-matching effect in different cohorts of kidney transplant recipients: 10 years later.

作者信息

Sasaki Nori, Idica Adam

机构信息

One Lambda Inc., Canoga Park, California, USA.

出版信息

Clin Transpl. 2010:261-82.

Abstract

Almost all the HLA-matching effects found by the 2000 analysis were confirmed by this study. The only HLA-matching effect found in the 2000 analysis that disappeared were those of "small matching effect" found in sub-populations of type I diabetes (PRA < 10%, donor age 20-35). The 2000 analysis found a lack of HLA matching effect in non-African American kidney transplant patients with type I diabetes between 1987 and 2000. The 2000 analysis found that a patients' ethnic group was a factor in graft survival; African American patients were found to have a significantly lower 10-year graft survival in the 5 or 6 mismatched group (27%) compared to Caucasian patients (40%). In addition, Asian patients (42%) had higher graft survival compared to that of Caucasian patients. In this study, we observe a similar pattern with death-censored graft analysis for all ethnic groups with 10-year graft survivals at 72.9% for Asians, 69.5% for Caucasians, and 49.3% for African Americans. There was an overall lack of HLA-matching effect on patient survival in the 2000 analysis. In our current analysis, the patient survivals remained virtually the same despite moderate increase in graft survival over the same period of time. The HLA-C locus mismatch was found to have additive effect to the 10-year graft survival trends observed in A and B mismatch cases. HLA-DQ mismatch on the other hand, showed limited HLA-matching effect and did not show the same additive effect as C. There are various possible issues in the DQ mismatch analysis, from the consistency of DQ typing results, lack of diversity in the DQ antigen, to the possibility of DQ mismatch having little effect on the graft survival. Utilizing kidney transplant cases performed from 1995 through 2000, the 2000 analysis projected 10-year survivals of 64% and 47% for the 0 ABDR mismatch and 5 or 6 ABDR mismatched cases respectively; the 2000 projection only missed actual death-censored survivals by 9% lower for the 0 mismatch and 17% lower for the 5 or 6 mismatch cases. Utilizing the transplant cases of 2005 through 2009, we projected their 10-year graft survivals for year 2020. The 10-year graft survival for 0 ABDR mismatched patients is expected to be over 85% and nearly 70% for 5 or 6 ABDR mismatched patients. The general upward trend of graft survival we have observed in the last 10 years has been dependent upon the development of novel transplant protocols and use of novel immunomodulatory reagents. This trend is likely to continue given the promise of new drugs and personalized healthcare. The decreasing range of the differences in the 10-year graft survival between best matched and worst matched HLA groups is also likely to continue. One interesting trend that is clearly evident is the increasing difference between the best and worst HLA-matching in terms of the associated graft half-life. The positive HLA-matching effect on long-term graft survival is clearly evident and should be taken into consideration for all kidney transplants.

摘要

2000年分析中发现的几乎所有HLA匹配效应均在本研究中得到证实。2000年分析中发现的唯一消失的HLA匹配效应是在I型糖尿病亚组(PRA<10%,供体年龄20 - 35岁)中发现的“小匹配效应”。2000年分析发现,1987年至2000年间,非裔美国I型糖尿病肾移植患者缺乏HLA匹配效应。2000年分析发现,患者的种族是移植物存活的一个因素;发现非裔美国患者在5或6个错配组中的10年移植物存活率(27%)显著低于白种人患者(40%)。此外,亚洲患者(42%)的移植物存活率高于白种人患者。在本研究中,我们对所有种族进行死亡审查的移植物分析时观察到类似模式,亚洲人的10年移植物存活率为72.9%,白种人为69.5%,非裔美国人为49.3%。2000年分析中,HLA匹配对患者存活总体上缺乏影响。在我们当前的分析中,尽管同期移植物存活率适度增加,但患者存活率基本保持不变。发现HLA - C位点错配对A和B错配病例中观察到的10年移植物存活趋势有累加效应。另一方面,HLA - DQ错配显示出有限的HLA匹配效应,且未显示出与C相同的累加效应。DQ错配分析存在各种可能的问题,从DQ分型结果的一致性、DQ抗原缺乏多样性,到DQ错配对移植物存活影响可能较小。利用1995年至2000年进行的肾移植病例,2000年分析预测0个ABDR错配和5或6个ABDR错配病例的10年存活率分别为64%和47%;2000年的预测对于0错配病例仅比实际死亡审查存活率低9%,对于5或6错配病例低17%。利用2005年至2009年的移植病例,我们预测了它们到2020年的10年移植物存活率。0个ABDR错配患者的10年移植物存活率预计超过85%,5或6个ABDR错配患者接近70%。我们在过去10年中观察到的移植物存活总体上升趋势依赖于新型移植方案的发展和新型免疫调节试剂的使用。鉴于新药和个性化医疗的前景,这一趋势可能会持续。最佳匹配和最差匹配HLA组之间10年移植物存活差异范围的缩小也可能会持续。一个明显的有趣趋势是,在相关移植物半衰期方面,最佳和最差HLA匹配之间的差异在增加。HLA匹配对长期移植物存活的积极影响明显,所有肾移植都应予以考虑。

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