肾移植急性排斥反应的通用尿细胞基因特征。
A universal urinary cell gene signature of acute rejection in kidney allografts.
机构信息
Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, USA; Department of Transplantation Medicine, NewYork-Presbyterian/Weill Cornell Medical Center, New York, NY, USA.
Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
出版信息
J Immunol Methods. 2024 Sep;532:113714. doi: 10.1016/j.jim.2024.113714. Epub 2024 Jun 25.
INTRODUCTION
Acute rejection (AR) undermines the life-extending benefits of kidney transplantation and is diagnosed using the invasive biopsy procedure. T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), or concurrent TCMR + ABMR (Mixed Rejection [MR]) are the three major types of AR. Development of noninvasive biomarkers diagnostic of AR due to any of the three types is a useful addition to the diagnostic armamentarium.
METHODS
We developed customized RT-qPCR assays and measured urinary cell mRNA copy numbers in 145 biopsy-matched urine samples from 126 kidney allograft recipients. We determined whether the urinary cell three-gene signature diagnostic of TCMR (Suthanthiran et al., 2013) discriminates patients with no rejection biopsies (NR, n = 50) from those with ABMR (n = 28) or MR (n = 20) biopsies.
RESULTS
The urinary cell three-gene signature discriminated all three types of rejection biopsies from NR biopsies (P < 0.0001, One-way ANOVA). Dunnett's multiple comparisons test yielded P < 0.0001 for NR vs. TCMR; P < 0.001 for NR vs. ABMR; and P < 0.0001 for NR vs. MR. By bootstrap resampling, optimism-corrected area under the receiver operating characteristic curve (AUC) was 0.749 (bias-corrected 95% confidence interval [CI], 0.638 to 0.840) for NR vs. TCMR (P < 0.0001); 0.780 (95% CI, 0.656 to 0.878) for NR vs. ABMR (P < 0.0001); and 0.857 (95% CI, 0.727 to 0.947) for NR vs. MR (P < 0.0001). All three rejection categories were distinguished from NR biopsies with similar accuracy (all AUC comparisons P > 0.05).
CONCLUSION
The urinary cell three-gene signature score discriminates AR due to TCMR, ABMR or MR from NR biopsies in human kidney allograft recipients.
简介
急性排斥反应（AR）削弱了肾移植的延长生命益处，并且通过侵入性活检程序进行诊断。T 细胞介导的排斥反应（TCMR）、抗体介导的排斥反应（ABMR）或同时发生的 TCMR+ABMR（混合排斥反应[MR]）是 AR 的三种主要类型。开发用于诊断任何三种类型的 AR 的非侵入性生物标志物是诊断工具的有益补充。
方法
我们开发了定制的 RT-qPCR 检测方法，并测量了 126 名肾移植受者的 145 个活检匹配尿液样本中的尿液细胞 mRNA 拷贝数。我们确定了诊断 TCMR 的尿液细胞三基因特征（Suthanthiran 等人，2013）是否可以区分无排斥活检（NR，n=50）与 ABMR（n=28）或 MR（n=20）活检患者。
结果
尿液细胞三基因特征可将所有三种类型的排斥活检与 NR 活检区分开来（P<0.0001，单向方差分析）。Dunnett 的多重比较检验得出 NR 与 TCMR 相比，P<0.0001；NR 与 ABMR 相比，P<0.001；NR 与 MR 相比，P<0.0001。通过自举重采样，NR 与 TCMR（P<0.0001）、NR 与 ABMR（P<0.0001）和 NR 与 MR（P<0.0001）的接收者操作特征曲线（ROC）的校正后曲线下面积（AUC）分别为 0.749（偏置校正 95%置信区间[CI]，0.638 至 0.840）。0.780（95%CI，0.656 至 0.878）用于 NR 与 ABMR（P<0.0001）；0.857（95%CI，0.727 至 0.947）用于 NR 与 MR（P<0.0001）。所有三种排斥类别均以相似的准确性与 NR 活检区分开来（所有 AUC 比较 P>0.05）。
结论
尿液细胞三基因特征评分可区分人类肾移植受者中由 TCMR、ABMR 或 MR 引起的 AR 与 NR 活检。
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