Bošnjak Matic, Večerić-Haler Željka, Pipan Tkalec Živa, Boštjančič Emanuela, Kojc Nika
Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia.
Department of Nephrology, University Medical Centre Ljubljana, Zaloška 7, 1000, Ljubljana, Slovenia.
Eur J Med Res. 2025 Jul 21;30(1):648. doi: 10.1186/s40001-025-02905-9.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune necrotizing small vessel vasculitis, frequently resulting in severe renal manifestations such as rapidly progressive glomerulonephritis (AAV-GN). Monitoring disease activity and determining ongoing renal involvement remain significant clinical challenges due to the limitations associated with traditional biomarkers. This study focused on the potential of circulating microRNA (miRNA) as supplementary noninvasive biomarkers for disease activity in AAV-GN.
This prospective follow-up study involved serum samples from 60 patients with biopsy-proven AAV-GN, collected at renal biopsy and at 3-, 6-, 12-, and 24-month intervals post-biopsy. Nine miRNAs (miR-21-3p, miR-30b/d/e-5p, miR-142-5p, miR-150-5p, miR-181a-5p, miR-181b-5p, and let-7a-5p) were selected based on the differential expressions in renal tissue and corresponding serum samples identified in the previous research phases. Expression analysis was performed using quantitative real-time polymerase chain reaction and correlated with disease activity based on the Birmingham Vasculitis Activity Score and other clinical parameters.
A significant correlation was identified between disease activity and the expression levels of the miR-30 family members and let-7a. Specifically, these miRNAs demonstrated consistent correlation patterns across follow-up samples independent of the time elapsed post-biopsy, with down-regulation correlating with the presence of active disease. Notably, the miRNA expression profile in partial remission appeared analogous to that of complete remission, suggesting that many patients categorized as having partial remission may, in fact, be considered in true clinical remission.
This study supports serum miRNA profiling as an adjunct noninvasive biomarker for assessing disease activity in AAV-GN. Such an approach could provide complementary information alongside traditional biomarkers and refine the future management of AAV-GN. However, it is important to acknowledge that our actual study cohort was small due to challenging technical aspects of miRNA expression analysis in the serum. Therefore, further research with larger cohorts is required to validate these results and assess their clinical applicability.
抗中性粒细胞胞浆抗体（ANCA）相关血管炎是一种自身免疫性坏死性小血管炎，常导致严重的肾脏表现，如快速进展性肾小球肾炎（AAV-GN）。由于传统生物标志物存在局限性，监测疾病活动和确定肾脏是否持续受累仍然是重大的临床挑战。本研究聚焦于循环微小RNA（miRNA）作为AAV-GN疾病活动补充性非侵入性生物标志物的潜力。
这项前瞻性随访研究纳入了60例经活检证实为AAV-GN患者的血清样本，这些样本在肾活检时以及活检后3、6、12和24个月时采集。基于前期研究阶段在肾组织及相应血清样本中鉴定出的差异表达，选择了9种miRNA（miR-21-3p、miR-30b/d/e-5p、miR-142-5p、miR-150-5p、miR-181a-5p、miR-181b-5p和let-7a-5p）。使用定量实时聚合酶链反应进行表达分析，并根据伯明翰血管炎活动评分和其他临床参数与疾病活动相关联。
疾病活动与miR-30家族成员和let-7a的表达水平之间存在显著相关性。具体而言，这些miRNA在随访样本中呈现出一致的相关模式，与活检后的时间无关，表达下调与活动性疾病的存在相关。值得注意的是，部分缓解期的miRNA表达谱与完全缓解期相似，这表明许多被归类为部分缓解的患者实际上可能处于真正的临床缓解状态。
本研究支持血清miRNA谱分析作为评估AAV-GN疾病活动的辅助非侵入性生物标志物。这种方法可以与传统生物标志物一起提供补充信息，并优化AAV-GN的未来管理。然而，必须认识到，由于血清中miRNA表达分析在技术方面具有挑战性，我们实际的研究队列规模较小。因此，需要更大队列的进一步研究来验证这些结果并评估其临床适用性。
