颈部淋巴结内免疫治疗季节性鼻结膜炎早期疗效与生物标志物分析的初步研究

文献信息

中文摘要

背景： 季节性过敏性鼻炎（SAR）造成显著的疾病负担，而淋巴结内免疫治疗（ILIT）为过敏原递送提供了一种靶向方法。然而，其短期疗效及相关生物标志物仍缺乏充分表征。
方法： 8例SAR患者接受超声引导下ILIT，将100 SQ-U过敏原提取物注射入颈部淋巴结。在基线、治疗后1个月和2个月进行评估，同时纳入8名年龄和性别匹配的健康对照。使用视觉模拟量表（VAS）和症状与药物联合评分（CSMSs）评估症状严重程度。对外周血单核细胞（PBMCs）进行转录组分析，鉴定差异表达基因（DEGs），随后进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析。还定量检测了血清特异性及总IgE水平，以及96种炎症蛋白。
结果： ILIT与1个月时VAS和CSMSs的显著降低相关，并在花粉高峰季节的2个月时持续改善。转录组分析鉴定出525个DEGs（p ≤ 0.05），反映从Th2优势反应向Th1和调节性T细胞（Treg）表型的转变。关键基因包括转录调节因子CREM、细胞因子IFNG、信号组分TNFAIP3以及趋化相关分子（CXCR5、CCR4、CCR6、TNFSF14、CCL20），确定了一个候选的早期ILIT反应多基因谱。血清蛋白质组分析显示CCL20下调和TNFRSF9上调，但这些蛋白变化与组织mRNA表达相关性较弱，且组间变异有限，表明其用于诊断或疗效评估的敏感性不足。
结论： ILIT在SAR中实现快速症状缓解，并具有免疫耐受诱导和先天免疫激活的转录组和蛋白质组证据。这些生物标志物可能支持早期疗效监测，值得在更大规模试验中确认。

英文摘要

BACKGROUND: Seasonal allergic rhinitis (SAR) imposes substantial morbidity, and intralymphatic immunotherapy (ILIT) offers a targeted approach for allergen delivery. However, short-term efficacy and associated biomarkers remain insufficiently characterized.
METHODS: Eight SAR patients received ultrasound-guided ILIT with 100 SQ-U allergen extracts injected into cervical lymph nodes. Assessments were performed at baseline, 1 month, and 2 months post-treatment, alongside eight age- and gender-matched healthy controls. Symptom severity was evaluated using Visual Analog Scale (VAS) and Combined Symptom and Medication Scores (CSMSs). Transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) identified differentially expressed genes (DEGs), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Serum levels of specific and total IgE, together with 96 inflammatory proteins, were also quantified.
RESULTS: ILIT was associated with significant reductions in VAS and CSMSs at one month, with sustained improvement at two months during peak pollen season. Transcriptomic analysis identified 525 DEGs (p ≤ 0.05), reflecting a shift from Th2-dominant response toward Th1 and regulatory T-cell (Treg) phenotypes. Key genes included transcriptional regulator CREM, cytokine IFNG, signaling component TNFAIP3, and chemotaxis-related molecules (CXCR5, CCR4, CCR6, TNFSF14, CCL20), identifying a candidate multi-gene profile of early ILIT response. Serum proteomic analysis showed downregulated CCL20 and upregulated TNFRSF9, though these protein changes correlated weakly with tissue mRNA expression and showed limited between-group variation, indicating insufficient sensitivity for diagnostic or efficacy assessment.
CONCLUSION: ILIT achieves rapid symptom relief in SAR, with transcriptomic and proteomic evidence of immune tolerance induction and innate immune activation. These biomarkers may support early efficacy monitoring, warranting confirmation in larger trials.