Balkan Ilker Inanç, Shahzadi Andleeb, Sönmez Haktan, Oktan Burhaneddin, Umar Muhammad Ihtisham, Mete Bilgül, Tabak Fehmi, Deniz Günnur, Küçüksezer Umut Can
Department of Immunology, Aziz Sancar Institute of Experimental Medicine, İstanbul University, İstanbul, Türkiye.
Institute of Graduate Studies in Health Sciences, İstanbul University, İstanbul, Türkiye.
Front Immunol. 2025 May 6;16:1565068. doi: 10.3389/fimmu.2025.1565068. eCollection 2025.
MicroRNAs (miRNAs), key regulators of cellular pathways, play crucial roles in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV). This study aimed to evaluate the expression and diagnostic potential of -identified miRNAs (miR-124-3p, miR-27a-3p, miR-548ac-3p, miR-3163) before and during antiretroviral treatment (ART), together with their correlations with immunological markers (CD4 count, CD4/CD45 ratio) and virological parameters (HIV RNA load).
Blood samples and clinical data of 16 patients were collected at 4 different time points; before the initiation of ART (baseline), 1, 2 and 6 months following HIV diagnosis. 16 healthy controls were enrolled to this study. RT-qPCR and ELISA techniques were used to analyze miRNA expression levels while immunological markers (CD4 count and ratio) were assessed by flow cytometry.
miR-27a-3p expression was significantly increased at 2 and 6 months of ART (p<0.001). miR-548ac-3p was upregulated at 6 month compared to healthy individuals and ART-naive subjects (p<0.05). miR-124-3p expression was significantly elevated in ART-naive subjects in comparison with healthy controls (p<0.001). Conversely, miR-3163 was downregulated in ART-naive, 1-month, and 2-month ART groups (p<0.001), but returned to normal levels by 6 months. miR-548ac-3p and miR-3163 showed moderate-to-strong positive correlations with CD4 counts (R=0.46, R=0.67; p<0.001). ROC analysis identified miR-3163 as a promising prognostic marker, with an AUC of 0.8561, (95% CI: 0.756-0.9265).
Our findings highlight the potential of miR-3163 as a robust prognostic biomarker for monitoring HIV progression and optimizing ART strategies. Validation in larger cohorts is warranted to confirm its clinical utility.
微小RNA（miRNA）是细胞通路的关键调节因子，在包括人类免疫缺陷病毒（HIV）在内的各种疾病的发病机制中发挥着关键作用。本研究旨在评估已鉴定的miRNA（miR-124-3p、miR-27a-3p、miR-548ac-3p、miR-3163）在抗逆转录病毒治疗（ART）前及治疗期间的表达及诊断潜力，以及它们与免疫标志物（CD4细胞计数、CD4/CD45比值）和病毒学参数（HIV RNA载量）的相关性。
收集16例患者在4个不同时间点的血样和临床数据，分别为ART开始前（基线）、HIV诊断后1个月、2个月和6个月。本研究纳入了16名健康对照。采用RT-qPCR和ELISA技术分析miRNA表达水平，同时通过流式细胞术评估免疫标志物（CD4细胞计数和比值）。
在ART治疗的第2个月和第6个月，miR-27a-3p表达显著升高（p<0.001）。与健康个体和未接受ART治疗的受试者相比，miR-548ac-3p在第6个月时上调（p<0.05）。与健康对照相比，未接受ART治疗的受试者中miR-124-3p表达显著升高（p<0.001）。相反，在未接受ART治疗、ART治疗1个月和2个月的组中，miR-3163表达下调（p<0.001），但在6个月时恢复到正常水平。miR-548ac-3p和miR-3163与CD4细胞计数呈中度至强正相关（R=0.46，R=0.67；p<0.001）。ROC分析确定miR-3163是一个有前景的预后标志物，AUC为0.8561（95%CI：0.756-0.9265）。
我们的研究结果突出了miR-3163作为监测HIV进展和优化ART策略的强大预后生物标志物的潜力。有必要在更大的队列中进行验证以确认其临床效用。
