Serum MicroRNA Transcriptomics and Acute Rejection or Recurrent Hepatitis C Virus in Human Liver Allograft Recipients: A Pilot Study.
Serum MicroRNA Transcriptomics and Acute Rejection or Recurrent Hepatitis C Virus in Human Liver Allograft Recipients: A Pilot Study.
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DOI：
10.1097/tp.0000000000003815
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发表时间：
2022-04-01
期刊：
影响因子：
6.2
通讯作者：
Suthanthiran M
中科院分区：
文献类型：
--
作者：
Muthukumar T;Akat KM;Yang H;Schwartz JE;Li C;Bang H;Ben-Dov IZ;Lee JR;Ikle D;Demetris AJ;Tuschl T;Suthanthiran M
急性排斥反应(AR)和复发性丙型肝炎病毒(R-丙型肝炎)是肝移植受者的重要并发症。移植物内病理的非侵入性诊断可能会改善他们的管理。我们对来自非免疫性、非病毒性(NINV)自然肝病患者的与移植肝活检相匹配的血清中的RNA进行了小RNA测序和miRNA微阵列分析。使用定制的RT-qPCR分析方法对91份与91份肝移植活检匹配的血清中的miRNAs的绝对水平进行了量化：26名独特的NINV患者的30份活检匹配的血清和41名独特的R-丙型肝炎患者的61份活检匹配的血清。通过Logistic回归和计算受检者工作特征曲线下面积，分析活检诊断与miRNA丰度的关系。9个miR-22、miR-34a、miR-122、miR-148A、miR-192、miR-193B、miR-194、miR-210和miR-885-5p与NINV-AR相关。对miRNA的绝对水平和预测者的拟合优度进行的Logistic回归分析表明，miR-34a+miR-210(P<；0.0001)的线性组合是最佳统计模型，而miR-122+miR-210(P<；0.0001)是包括miR-122的最佳模型。不同的线性组合miR-34a+miR-210(P<；0.0001)是鉴别NINV-AR和R型丙型肝炎合并移植物内炎症的最佳模式，miR-34a+miR-122(P<；0.0001)是鉴别NINV-AR和R型丙型肝炎合并移植物内纤维化的最佳模式。利用定制化RT-qPCR定量检测循环中miRNAs的水平，可能提供一种快速和非侵入性的手段来诊断人同种异体肝移植物中的AR，并用于区分AR与因复发的丙型肝炎病毒引起的移植物内炎症或纤维化。ClinicalTrials.gov标识：NCT01428700
Acute rejection (AR) and recurrent HCV (R-HCV) are significant complications in liver allograft recipients. Noninvasive diagnosis of intragraft pathologies may improve their management. We performed small RNA sequencing and miRNA microarray profiling of RNA from sera matched to liver allograft biopsies from patients with nonimmune, nonviral (NINV) native liver disease. Absolute levels of informative miRNAs in 91 sera matched to 91 liver allograft biopsies were quantified using customized RT-qPCR assays: 30 biopsy-matched sera from 26 unique NINV patients and 61 biopsy-matched sera from 41 unique R-HCV patients. The association between biopsy diagnosis and miRNA abundance was analyzed by logistic regression and calculating the area under the receiver operating characteristic curve. Nine miRNAs- miR-22, miR-34a, miR-122, miR-148a, miR-192, miR-193b, miR-194, miR-210 and miR-885–5p- were identified by both sRNA-seq and TLDA to be associated with NINV-AR. Logistic regression analysis of absolute levels of miRNAs and goodness-of-fit of predictors identified a linear combination of miR-34a + miR-210 (P<0.0001) as the best statistical model and miR-122 + miR-210 (P<0.0001) as the best model that included miR-122. A different linear combination of miR-34a + miR-210 (P<0.0001) was the best model for discriminating NINV-AR from R-HCV with intragraft inflammation, and miR-34a + miR-122 (P<0.0001) was the best model for discriminating NINV-AR from R-HCV with intragraft fibrosis. Circulating levels of miRNAs, quantified using customized RT-qPCR assays, may offer a rapid and noninvasive means of diagnosing AR in human liver allografts and for discriminating AR from intragraft inflammation or fibrosis due to recurrent HCV. ClinicalTrials.gov identifier: NCT01428700