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两种移植前脱敏方案对肾移植存活率及供体特异性抗体产生的影响

Effects of Two Preemptive Post-transplant Desensitization Regimens Upon Renal Allograft Survival and DSA Elaboration.

作者信息

Kimball Pamela M, McDougan Felecia A, King Anne

出版信息

Clin Transpl. 2014:197-203.

Abstract

We used a simple point-based algorithm to identify patients who might benefit from desensitization because of their higher risk of antibody-mediated chronic rejection and graft failure. Points were assigned to known but easily determined risk factors (panel reactive antibody, flow crossmatch, delayed graft function) and calculated immediately after deceased donor kidney transplantation. Point totals were used to identify: 1) which patients would receive desensitization; and, 2) which regimen each patient would receive. This standardized approached resulted in improved overall graft survival in both modalities compared to historically untreated sensitized patients. While preemptive desensitization positively impacted clinical metrics, the improvements were unequal between regimens. PP/IVIG treatment clearly resulted in greater elimination of preexisting donor specific antibodies against HLA antigens (DSA), fewer late rejections, and superior 3-year graft survival among patients who resolved their DSA as well as those with persistent DSA. Since graft survival among PP/IVIG recipients was excellent even when preexisting DSA were still present one year post-transplant, it suggests that the benefit of this regimen is two-fold: first to increase DSA elimination among patients, and secondly, to minimize downstream immune activating events such as rejection. In contrast, IVIG patients with persistent DSA had more rejections and graft survival only slightly better than if they had no treatment at all. Since the IVIG group also had a preponderance of Class II directed DSA, we cannot discount the influence of that specificity upon graft outcomes. Additional studies are needed to confirm our findings and to allow more effective assessment of the impact of DSA specificity upon desensitization efficacy and graft success.

摘要

我们使用了一种简单的基于积分的算法来识别那些因抗体介导的慢性排斥反应和移植失败风险较高而可能从脱敏治疗中获益的患者。积分被分配给已知但易于确定的风险因素(群体反应性抗体、流式细胞交叉配型、移植肾功能延迟),并在 deceased 供体肾移植后立即计算。积分总和用于确定:1)哪些患者将接受脱敏治疗;以及 2)每位患者将接受哪种治疗方案。与历史上未经治疗的致敏患者相比,这种标准化方法在两种治疗方式中均提高了总体移植存活率。虽然抢先脱敏对临床指标产生了积极影响,但不同治疗方案之间的改善并不均衡。PP/IVIG 治疗明显导致针对 HLA 抗原的预先存在的供体特异性抗体(DSA)消除得更多,晚期排斥反应更少,并且在解决了 DSA 的患者以及持续存在 DSA 的患者中 3 年移植存活率更高。由于即使移植后一年仍存在预先存在的 DSA,PP/IVIG 接受者的移植存活率仍很高,这表明该治疗方案的益处有两方面:首先是增加患者体内 DSA 的消除,其次是将诸如排斥反应等下游免疫激活事件降至最低。相比之下,持续存在 DSA 的 IVIG 患者有更多的排斥反应,移植存活率仅略高于未接受任何治疗的情况。由于 IVIG 组中也有大量针对 II 类抗原的 DSA,我们不能忽视该特异性对移植结果的影响。需要更多的研究来证实我们的发现,并更有效地评估 DSA 特异性对脱敏疗效和移植成功的影响。

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