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慢性持续性抗体介导的排斥反应与间质而不是肾小球转录物的上调有关。

Chronic Active Antibody-Mediated Rejection Is Associated With the Upregulation of Interstitial But Not Glomerular Transcripts.

机构信息

Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czechia.

Department of Clinical and Transplant Pathology, Institute for Clinical and Experimental Medicine, Prague, Czechia.

出版信息

Front Immunol. 2021 Sep 20;12:729558. doi: 10.3389/fimmu.2021.729558. eCollection 2021.

Abstract

Molecular assessment of renal allografts has already been suggested in antibody-mediated rejection (ABMR), but little is known about the gene transcript patterns in particular renal compartments. We used laser capture microdissection coupled with quantitative RT-PCR to distinguish the transcript patterns in the glomeruli and tubulointerstitium of kidney allografts in sensitized retransplant recipients at high risk of ABMR. The expressions of 13 genes were quantified in biopsies with acute active ABMR, chronic active ABMR, acute tubular necrosis (ATN), and normal findings. The transcripts were either compartment specific ( in the glomeruli and and in the tubulointerstitium), ABMR specific (), or follow-up specific ( and ). The transcriptional profiles of early acute ABMR shared similarities with ATN. The transcripts of and increased in the glomeruli in both acute ABMR and chronic active ABMR. Chronic active ABMR was associated with the upregulation of most genes (, , , , , , and ) in the tubulointerstitium. In this study, we show distinct gene expression patterns in specific renal compartments reflecting cellular infiltration observed by conventional histology. In comparison with active ABMR, chronic active ABMR is associated with increased transcripts of tubulointerstitial origin.

摘要

分子评估已在抗体介导的排斥反应(ABMR)中提出,但对于特定肾单位的基因转录模式知之甚少。我们使用激光捕获显微切割和实时定量 RT-PCR 来区分致敏再移植受者高 ABMR 风险的肾移植中肾小球和肾小管间质的转录模式。在急性活动 ABMR、慢性活动 ABMR、急性肾小管坏死 (ATN) 和正常发现的活检中定量了 13 个基因的表达。转录物要么是特定于肾单位的(在肾小球中为 ,在肾小管间质中为 ),要么是 ABMR 特异性的(),要么是随访特异性的(和)。早期急性 ABMR 的转录谱与 ATN 相似。在急性 ABMR 和慢性活动 ABMR 中,肾小球中的 和 转录物均增加。慢性活动 ABMR 与大多数基因(、、、、、、和)在肾小管间质中的上调有关。在这项研究中,我们展示了特定肾单位中反映常规组织学观察到的细胞浸润的独特基因表达模式。与活动 ABMR 相比,慢性活动 ABMR 与肾小管间质来源的转录物增加有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56af/8488163/e333d1d237ff/fimmu-12-729558-g001.jpg

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