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

Clinical transplants Pub Date : 2014-01-01
Pamela M Kimball, Felecia A McDougan, Anne King
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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.

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两种先发制人的移植后脱敏方案对同种异体肾移植存活和DSA细化的影响。
我们使用一种简单的基于点的算法来识别可能受益于脱敏的患者,因为他们抗体介导的慢性排斥和移植失败的风险更高。对已知但容易确定的危险因素(面板反应性抗体、血流交叉匹配、移植延迟功能)进行评分,并在死亡供体肾移植后立即计算。使用积分来确定:1)哪些患者将接受脱敏治疗;2)每个病人将接受哪种治疗方案。与历史上未治疗的致敏患者相比,这种标准化的方法提高了两种方式的总体移植物存活率。虽然先发制人的脱敏对临床指标有积极影响,但不同方案的改善是不平等的。PP/IVIG治疗明显能更好地消除先前存在的针对HLA抗原的供体特异性抗体(DSA),减少晚期排斥反应,在解决了DSA的患者和持续性DSA的患者中,3年移植物生存率更高。由于PP/IVIG受者的移植存活非常好,即使在移植一年后仍然存在DSA,这表明该方案的益处是双重的:首先增加患者的DSA消除,其次减少下游免疫激活事件,如排斥反应。相比之下,持续DSA的IVIG患者有更多的排斥反应,移植物存活率仅略高于未接受治疗的患者。由于IVIG组也有II类定向DSA的优势,我们不能忽视这种特异性对移植物结果的影响。需要进一步的研究来证实我们的发现,并允许更有效地评估DSA特异性对脱敏效果和移植成功的影响。
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HLA Matching The Lazarus phenomenon. HLA Epitopes and Shared Molecular Eplet Characterization and Their Implication on Transplant Outcome: The Experience of One Center. Acute Rejection, Kidney Allograft Function, and Graft Survival in Patients with Circulating Pre-Transplant IgG Antibodies Directed Against Donor HLA-A, -B, or -C Locus Determined Antigens. Pre-empting Antibody-Mediated Rejection: A Program of DSA Monitoring and Treatment Can Effectively Prevent Antibody Mediated Rejection.
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