Iwasaki Kenta, Yamamoto Takayuki, Inanaga Yukiko, Hiramitsu Takahisa, Miwa Yuko, Murotani Kenta, Narumi Shuji, Watarai Yoshihiko, Katayama Akio, Uchida Kazuharu, Kobayashi Takaaki
a Department of Kidney Disease and Transplant Immunology , Aichi Medical University , Nagakute , Japan.
b Department of Transplant Surgery , Nagoya Daini Red Cross Hospital , Nagoya , Japan.
Biomarkers. 2017 Feb;22(1):45-54. doi: 10.1080/1354750X.2016.1204000. Epub 2016 Jul 7.
De novo donor-specific HLA antibody (DSA) would not necessarily contribute to chronic antibody-mediated rejection (CAMR) in kidney transplantation. Here, we investigated whether PBMC miRNAs could be predictable biomarkers for CAMR. Microarray profiling of 435 mature miRNAs in pooled samples was conducted. Individual analysis revealed that miR-142-5p was significantly (p < 0.01) underexpressed in patients with DSA. After DSA production, miR-486-5p and its target PTEN/foxO3 mRNA were significantly overexpressed (p < 0.01) and underexpressed (p < 0.01), respectively, in patients with biopsy-proven CAMR, compared with non-CAMR. Our studies suggest that miRNA expression patterns may serve as noninvasive diagnostic biomarkers to evaluate immune response and kidney allograft status.
新生供者特异性HLA抗体(DSA)不一定会导致肾移植中的慢性抗体介导排斥反应(CAMR)。在此,我们研究了外周血单个核细胞(PBMC)中的微小RNA(miRNA)是否可作为CAMR的预测性生物标志物。我们对混合样本中的435种成熟miRNA进行了微阵列分析。个体分析显示,DSA患者中miR-142-5p显著低表达(p < 0.01)。与非CAMR患者相比,在经活检证实为CAMR的患者中,DSA产生后,miR-486-5p及其靶标PTEN/foxO3 mRNA分别显著高表达(p < 0.01)和低表达(p < 0.01)。我们的研究表明,miRNA表达模式可作为非侵入性诊断生物标志物,用于评估免疫反应和肾移植状态。