Bošnjak Matic, Večerić-Haler Željka, Pipan Tkalec Živa, Tomšič Jakob, Boštjančič Emanuela, Kojc Nika
Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Department of Nephrology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Front Immunol. 2025 Jul 17;16:1599043. doi: 10.3389/fimmu.2025.1599043. eCollection 2025.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing small vessel vasculitis that frequently manifests as glomerulonephritis (AAV-GN). An accurate noninvasive biomarker reflecting active AAV-GN remains elusive. The knowledge of microRNAs (miRNAs), which have been considered as disease-specific biomarkers, is scarce and lacks validated data in AAV.
This study validated a renal tissue expression profile of candidate miRNAs specific to AAV-GN selected through prior screening using independent cohorts. The analysis was extended to serum samples to explore the potential of a circulating miRNA panel as a noninvasive biomarker for active AAV-GN. To substantiate the findings, we correlated the molecular data with clinical and histologic markers of AAV-GN activity.
We identified , and as potential biomarkers distinguishing AAV-GN from non-AAV renal diseases and healthy controls. In addition, and correlated with the presence of active AAV-GN, while differentiated AAV-GN subtypes based on ANCA antigen specificity. ROC curve analysis demonstrated that the combined serum expression of and reliably distinguished AAV-GN from other renal pathologies, including ANCA-positive cases without histologic evidence of AAV-GN.
Our findings highlight the potential of circulating miRNA expression signature as a noninvasive biomarker for ongoing AAV-GN in the appropriate setting. Larger confirmatory studies are essential to support the clinical application of miRNA-based biomarkers in AAV-GN diagnostics and disease monitoring.
抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）的特征是坏死性小血管炎，常表现为肾小球肾炎（AAV-GN）。目前仍缺乏一种准确反映活动性AAV-GN的非侵入性生物标志物。微小RNA（miRNA）被认为是疾病特异性生物标志物，但在AAV中相关知识匮乏且缺乏经过验证的数据。
本研究通过独立队列对先前筛选出的AAV-GN特异性候选miRNA的肾组织表达谱进行了验证。分析扩展至血清样本，以探索循环miRNA组合作为活动性AAV-GN非侵入性生物标志物的潜力。为证实研究结果，我们将分子数据与AAV-GN活动性的临床和组织学标志物进行了关联。
我们鉴定出[具体miRNA名称1]、[具体miRNA名称2]和[具体miRNA名称3]作为区分AAV-GN与非AAV肾脏疾病及健康对照的潜在生物标志物。此外，[具体miRNA名称4]和[具体miRNA名称5]与活动性AAV-GN的存在相关，而[具体miRNA名称6]根据ANCA抗原特异性区分AAV-GN亚型。ROC曲线分析表明，[具体miRNA名称4]和[具体miRNA名称5]的血清联合表达能够可靠地区分AAV-GN与其他肾脏疾病，包括无AAV-GN组织学证据的ANCA阳性病例。
我们的研究结果突出了循环miRNA表达特征作为在适当情况下活动性AAV-GN非侵入性生物标志物的潜力。更大规模的验证性研究对于支持基于miRNA的生物标志物在AAV-GN诊断和疾病监测中的临床应用至关重要。
