Reducing De Novo Donor-Specific Antibody Levels during Acute Rejection Diminishes Renal Allograft Loss

Reducing De Novo Donor-Specific Antibody Levels during Acute Rejection Diminishes Renal Allograft Loss
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DOI:
10.1111/j.1600-6143.2009.02577.x
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发表时间:
2009-05-01
影响因子:
8.8
通讯作者:
Woodle, E. S.
Woodle, E. S.
中科院分区:
医学2区
文献类型:
--
作者:
Everly, M. J.;Everly, J. J.;Woodle, E. S.

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分析急性细胞性排斥反应(ACR)时检测的DSA水平和DSA水平对排斥反应治疗的反应对移植肾存活的影响。患有急性排斥反应的肾移植患者在排斥反应诊断时接受DSA检测,使用Luminex单抗原珠定量DSA水平。52例患者发生急性排斥反应,其中16例(31%)新发DSA检测阳性。中位随访时间为急性排斥反应后27.0 ± 17.4个月。影响同种异体移植物存活的因素的单变量分析显示,非裔美国人种族、DGF、细胞毒性PRA > 20%(当前)和/或> 50%(峰值)、从头DSA、C4d和重复移植具有显著性。多变量分析显示,仅新发DSA(同种异体移植物丢失风险增加6.6倍,p = 0.017)具有显著性。4年移植物存活率ACR(无DSA)(100%)高于混合性急性排斥反应(ACR + DSA/C4d)(65%)或抗体介导的排斥反应(35%)(p < 0.001)。14天内DSA减少> 50%的患者的同种异体移植物存活率较高(p = 0.039)。在排斥反应时检测到的新生DSA与同种异体移植物存活率降低相关,但迅速减少DSA与同种异体移植物存活率提高相关。DSA应被视为一个潜在的新的排斥治疗终点。
The effect of de novo DSA detected at the time of acute cellular rejection (ACR) and the response of DSA levels to rejection therapy on renal allograft survival were analyzed. Kidney transplant patients with acute rejection underwent DSA testing at rejection diagnosis with DSA levels quantified using Luminex single-antigen beads. Fifty-two patients experienced acute rejection with 16 (31%) testing positive for de novo DSA. Median follow-up was 27.0 +/- 17.4 months postacute rejection. Univariate analysis of factors influencing allograft survival demonstrated significance for African American race, DGF, cytotoxic PRA > 20% (current) and/or > 50% (peak), de novo DSA, C4d and repeat transplantation. Multivariate analysis showed only de novo DSA (6.6-fold increased allograft loss risk, p = 0.017) to be significant. Four-year allograft survival was higher with ACR (without DSA) (100%) than mixed acute rejection (ACR with DSA/C4d) (65%) or antibody-mediated rejection (35%) (p < 0.001). Patients with > 50% reduction in DSA within 14 days experienced higher allograft survival (p = 0.039). De novo DSAs detected at rejection are associated with reduced allograft survival, but prompt DSA reduction was associated with improved allograft survival. DSA should be considered a potential new end point for rejection therapy.