Prognostic value of the donor-derived cell-free DNA assay in acute renal rejection therapy: A prospective cohort study
Prognostic value of the donor-derived cell-free DNA assay in acute renal rejection therapy: A prospective cohort study
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供体来源的游离细胞 DNA 测定在急性肾排斥治疗中的预后价值：一项前瞻性队列研究
DOI：
10.1111/ctr.14053
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发表时间：
2020-09-04
影响因子：
2.1
通讯作者：
Wang, Rending
中科院分区：
文献类型：
--
作者：
Shen, Jia;Guo, Luying;Wang, Rending
供体来源的细胞游离DNA（dd-cfDNA）是用于监测同种异体移植物状态的有前景的生物标志物。然而，dd-cfDNA是否能实时反映抗排斥治疗效果仍不清楚。我们前瞻性招募了28例急性肾排斥反应患者，其中5例为ABMR，12例为IA或IB型排斥反应，11例为IIA或IIB型排斥反应。使用人单核苷酸多态性（SNP）基因座捕获杂交测量外周血中的dd-cfDNA水平。抗排斥治疗后，dd-cfDNA百分比（dd-cfDNA%）从2.566 +/- 0.549%显著下降至0.773 +/- 0.116%（P <0.001）。在每日注射甲泼尼龙的3天过程中，dd-cfDNA%稳定下降，但在抗排斥治疗结束时和2周后未观察到dd-cfDNA%的显著差异。dd-cfDNA%的变化（dd-cfDNA%增量）与治疗后1个月（rho = 2.570，P = 0.022）、3个月（rho = 3.210，P = 0.027）和6个月（rho = 2.860，P = 0.019）的估计肾小球滤过率正相关。因此，dd-cfDNA测定显示了治疗结果和同种异体移植物恢复的预后能力;然而，无论排斥类型如何，其能力都被甲泼尼龙抑制。此外，需要重新评估测试的频率间隔。
Donor-derived cell-free DNA (dd-cfDNA) is a promising biomarker for monitoring allograft status. However, whether dd-cfDNA can reflect real-time anti-rejection treatment effects remains unclear. We prospectively recruited 28 patients with acute renal rejection, including 5 with ABMR, 12 with type IA or type IB rejection, and 11 with type IIA or IIB rejection. dd-cfDNA levels in peripheral blood were measured using human single nucleotide polymorphism (SNP) locus capture hybridization. The percentage of dd-cfDNA (dd-cfDNA%) declined significantly from 2.566 +/- 0.549% to 0.773 +/- 0.116% (P < .001) after anti-rejection therapy. The dd-cfDNA% decreased steadily over the course of 3 days with daily methylprednisolone injections, but no significant difference in the dd-cfDNA% was observed between the end of anti-rejection therapy and 2 weeks later. Changes in the dd-cfDNA% ( increment dd-cfDNA%) demonstrated a positive correlation with estimated glomerular filtration rates at 1 month (rho = 2.570,P = .022), 3 months (rho = 3.210,P = .027), and 6 months (rho = 2.860,P = .019) after therapy. Thus, the dd-cfDNA assay shows prognostic capabilities in therapy outcome and allograft recovery; however, its ability is inhibited by methylprednisolone regardless of the types of rejection. Additionally, a reassessment of frequency intervals for testing is required.