Abstract：
BACKGROUND: 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).
CONCLUSIONS: The urinary cell three-gene signature score discriminates AR due to TCMR, ABMR or MR from NR biopsies in human kidney allograft recipients.
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).
CONCLUSIONS: The urinary cell three-gene signature score discriminates AR due to TCMR, ABMR or MR from NR biopsies in human kidney allograft recipients.
摘要：
背景：急性排斥反应（AR）破坏了肾移植的延长寿命的益处，并使用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），或并发TCMR+ABMR(混合排斥[MR])是AR的三种主要类型。由于这三种类型中的任何一种，开发诊断AR的非侵入性生物标志物是诊断设备的有用补充。
方法：我们开发了定制的RT-qPCR检测方法，并测量了来自126个肾脏同种异体移植受者的145个活检匹配尿液样本中的尿细胞mRNA拷贝数。我们确定了尿细胞三基因签名是否可以诊断TCMR（Suthanthiran等人。,2013)区分无排斥活检的患者(NR，n=50）来自ABMR（n=28）或MR（n=20）活检的患者。
结果：尿细胞三基因签名将所有三种类型的排斥活检与NR活检区分开（P<0.0001，单因素方差分析）。Dunnett的多重比较检验得出NR与NR的P<0.0001TCMR；NR与NR的P<0.001ABMR；NR与NR的P<0.0001MR.通过引导重采样，乐观校正的受试者工作特征曲线下面积（AUC）为0.749（偏差校正的95％置信区间[CI]，0.638to0.840)forNRvs.TCMR（P<0.0001）；NR与NR的0.780（95％CI，0.656至0.878）ABMR（P<0.0001）；NR与NR的关系为0.857（95％CI，0.727至0.947）MR(P<0.0001)。所有三个排斥类别均以相似的准确性与NR活检区分开(所有AUC比较P>0.05)。
结论：尿细胞三基因签名评分区分AR是由于TCMR，来自人肾脏同种异体移植受体NR活检的ABMR或MR。
方法：我们开发了定制的RT-qPCR检测方法，并测量了来自126个肾脏同种异体移植受者的145个活检匹配尿液样本中的尿细胞mRNA拷贝数。我们确定了尿细胞三基因签名是否可以诊断TCMR（Suthanthiran等人。,2013)区分无排斥活检的患者(NR，n=50）来自ABMR（n=28）或MR（n=20）活检的患者。
结果：尿细胞三基因签名将所有三种类型的排斥活检与NR活检区分开（P<0.0001，单因素方差分析）。Dunnett的多重比较检验得出NR与NR的P<0.0001TCMR；NR与NR的P<0.001ABMR；NR与NR的P<0.0001MR.通过引导重采样，乐观校正的受试者工作特征曲线下面积（AUC）为0.749（偏差校正的95％置信区间[CI]，0.638to0.840)forNRvs.TCMR（P<0.0001）；NR与NR的0.780（95％CI，0.656至0.878）ABMR（P<0.0001）；NR与NR的关系为0.857（95％CI，0.727至0.947）MR(P<0.0001)。所有三个排斥类别均以相似的准确性与NR活检区分开(所有AUC比较P>0.05)。
结论：尿细胞三基因签名评分区分AR是由于TCMR，来自人肾脏同种异体移植受体NR活检的ABMR或MR。
