Sublingual immunotherapy (SLIT) is an effective treatment for allergic rhinitis (AR), but its efficacy is variable among individuals. This study aimed to characterize serum exosome-derived microRNAs (miRNAs) and evaluate their abilities in predicting the efficacy of SLIT in AR. RNA sequencing was performed to explore differentially expressed exosomal miRNAs in serum exosomes between AR patients and healthy controls (HCs). Sequencing analysis results were verified in an independent cohort, and the correlations between the levels of exosome-derived miRNAs and disease severity were evaluated. The most promising miRNAs were further tested in two AR cohorts treated with SLIT to assess their abilities in predicting short and long-term efficacy, respectively. The exosome-derived miRNAs profiling in the AR group was significantly different from the HC group, and differentially expressed genes were enriched and clustered in pathways such as PI3K-Akt and ErbB signalling pathways. The top three most significant miRNAs were verified by reverse transcription-polymerase chain reaction (qRT-PCR), and results showed that miR-146a-3p levels were significantly elevated in the AR group and correlated with the total and specific gE levels, the visual analogue scale of the total nasal symptom score (all p < 0.05). Further data in the first validation cohort suggested that miR-146a-3p levels were significantly downregulated in the effective group, and logistic regression showed that miR-146a-3p levels were associated with the short-term efficacy of SLIT(p < 0.05). The receiver operating characteristic (ROC) curve showed that miR-146a-3p could early predict SLIT efficacy (AUC = 0.669, p = 0.047). In the second validation cohort, miR-146a-3p levels were also decreased in the effective group and the ROC curve further confirmed its reliable accuracy in predicting the long-term efficacy of SLIT in AR patients (AUC = 0.749, p < 0.001). Serum exosome-derived miRNAs may be involved in the development of AR and associated with its disease severity. Serum exosome-derived miR-146a-3p seems to be a novel biomarker for predicting the short and long-term efficacies of SLIT in AR patients.

中文翻译：

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血清外泌体 miR-146a-3p 与过敏性鼻炎的疾病严重程度和舌下免疫治疗的疗效相关

舌下免疫疗法（SLIT）是治疗过敏性鼻炎（AR）的有效方法，但其疗效因人而异。本研究旨在表征血清外泌体衍生的 microRNA (miRNA) 并评估其预测 SLIT 在 AR 中的疗效的能力。通过 RNA 测序来探索 AR 患者和健康对照 (HC) 之间血清外泌体中差异表达的外泌体 miRNA。测序分析结果在独立队列中得到验证，并评估了外泌体衍生的 miRNA 水平与疾病严重程度之间的相关性。最有希望的 miRNA 在接受 SLIT 治疗的两个 AR 队列中进行了进一步测试，以分别评估它们预测短期和长期疗效的能力。AR组中外泌体来源的miRNA谱与HC组显着不同，差异表达基因在PI3K-Akt和ErbB信号通路等通路中富集和聚集。通过逆转录聚合酶链反应（qRT-PCR）验证了前三个最显着的 miRNA，结果显示 miR-146a-3p 水平在 AR 组中显着升高，并与总 gE 水平和特异性 gE 水平相关，视觉鼻部症状总评分的模拟量表（所有 p < 0.05）。第一个验证队列的进一步数据表明，有效组中 miR-146a-3p 水平显着下调，逻辑回归显示 miR-146a-3p 水平与 SLIT 的短期疗效相关（p < 0.05）。受试者工作特征（ROC）曲线显示miR-146a-3p可以早期预测SLIT疗效（AUC = 0.669，p = 0.047）。在第二个验证队列中，有效组中的 miR-146a-3p 水平也有所下降，ROC 曲线进一步证实了其在预测 SLIT 对 AR 患者长期疗效方面的可靠准确性（AUC = 0.749，p < 0.001）。血清外泌体衍生的 miRNA 可能参与 AR 的发展并与其疾病严重程度相关。血清外泌体衍生的 miR-146a-3p 似乎是预测 SLIT 对 AR 患者短期和长期疗效的新型生物标志物。