Department of Nephrology, Charité University Medicine Berlin, Berlin, Germany.
Deutsches Rheuma-Forschungszentrum Berlin, A Leibniz Institute(DRFZ), Berlin, Germany.
Clin Transplant. 2018 Dec;32(12):e13429. doi: 10.1111/ctr.13429. Epub 2018 Nov 18.
Antibody-mediated rejection (ABMR) after kidney transplantation (KTx) remains the crucial obstacle to successful long-term graft function. The identification of gene signatures involved in ABMR could grant the basis for better prevention and treatment strategies.
The identification of gene signatures in whole blood cells specific for ABMR after KTx.
Total RNA from blood cells of 16 kidney-transplanted patients with ABMR, stable graft function (SGF), and with T-cell-mediated rejection (TCMR) was isolated. Gene expression was determined by high-throughput sequencing followed by validation and analyses of differentially expressed candidates on mRNA level and on protein level in a large patient cohort (n = 185) in patients with SGF, urinary tract infection (UTI), borderline rejection (BL), TCMR, ABMR, and interstitial fibrosis and tubular atrophy.
From the 570 genes detected, 111 discriminated ABMR from SGF and TCMR. A distinct enrichment of interferon (IFN) type I and type II signature gene set was observed. The expression of candidate genes IFIT1, ETV7, and RSAD2 distinguished ABMR patients from patients with SGF and also TCMR, whereas ETV7 and RSAD2 differentiated ABMR also from BL.
The IFN-inducible genes ETV7 and RSAD2 represent specific biomarkers for ABMR episodes after KTx.
肾移植（KTx）后抗体介导的排斥反应（ABMR）仍然是成功实现长期移植物功能的关键障碍。鉴定与 ABMR 相关的基因特征可为更好的预防和治疗策略提供基础。
鉴定 KTx 后全血中针对 ABMR 的基因特征。
从 16 名发生 ABMR、稳定移植物功能（SGF）和 T 细胞介导排斥反应（TCMR）的肾移植患者的血液中分离出总 RNA。通过高通量测序确定基因表达，然后在 SGF、尿路感染（UTI）、边界性排斥（BL）、TCMR、ABMR 和间质纤维化和肾小管萎缩的大患者队列（n=185）中验证和分析差异表达候选物的 mRNA 水平和蛋白水平。
从检测到的 570 个基因中，有 111 个基因区分了 ABMR 与 SGF 和 TCMR。观察到干扰素（IFN）I 型和 II 型特征基因集的明显富集。候选基因 IFIT1、ETV7 和 RSAD2 的表达将 ABMR 患者与 SGF 患者以及 TCMR 患者区分开来，而 ETV7 和 RSAD2 也将 ABMR 与 BL 区分开来。
IFN 诱导基因 ETV7 和 RSAD2 是 KTx 后 ABMR 发作的特异性生物标志物。
