Bošnjak Matic, Večerić-Haler Željka, Boštjančič Emanuela, Kojc Nika
Faculty of Medicine, Institute of Pathology, University of Ljubljana, Korytkova Ulica 2, 1000 Ljubljana, Slovenia.
Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2021 Dec 22;23(1):105. doi: 10.3390/ijms23010105.
Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises autoimmune disease entities that cause target organ damage due to relapsing-remitting small vessel necrotizing vasculitis, and which affects various vascular beds. The pathogenesis of AAV is incompletely understood, which translates to considerable disease- and treatment-related morbidity and mortality. Recent advances have implicated microRNAs (miRNAs) in AAV; however, their accurate characterization in renal tissue is lacking. The goal of this study was to identify the intrarenal miRNA expression profile in AAV relative to healthy, non-inflammatory and inflammatory controls to identify candidate-specific miRNAs. Formalin-fixed, paraffin-embedded renal biopsy tissue samples from 85 patients were obtained. Comprehensive miRNA expression profiles were performed using panels with 752 miRNAs and revealed 17 miRNA that differentiated AAV from both controls. Identified miRNAs were annotated to characterize their involvement in pathways and to define their targets. A considerable subset of differentially expressed miRNAs was related to macrophage and lymphocyte polarization and cytokines previously deemed important in AAV pathogenesis, lending credence to the obtained results. Interestingly, several members of the miR-30 family were detected. However, a validation study of these differentially expressed miRNAs in an independent, larger sample cohort is needed to establish their potential diagnostic utility.
抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）是一类自身免疫性疾病，因小血管坏死性血管炎的复发-缓解导致靶器官损害，且累及多个血管床。AAV的发病机制尚未完全明确，这导致了与疾病和治疗相关的较高发病率和死亡率。最近的研究进展表明微小RNA（miRNA）与AAV有关；然而，在肾组织中对它们的准确特征描述尚缺乏。本研究的目的是确定AAV相对于健康、非炎症和炎症对照的肾内miRNA表达谱，以鉴定候选特异性miRNA。获取了85例患者的福尔马林固定、石蜡包埋的肾活检组织样本。使用包含752种miRNA的芯片进行了全面的miRNA表达谱分析，结果显示有17种miRNA可将AAV与两种对照区分开来。对鉴定出的miRNA进行注释，以表征它们在信号通路中的作用并确定其靶标。相当一部分差异表达的miRNA与巨噬细胞和淋巴细胞极化以及先前认为在AAV发病机制中重要的细胞因子有关，这为所得结果提供了可信度。有趣的是，检测到了miR-30家族的几个成员。然而，需要在一个独立的、更大样本队列中对这些差异表达的miRNA进行验证研究，以确定它们潜在的诊断效用。
