关键词: Allergic rhinitis Blimp1 Sublingual immunotherapy Tolerance Treg

Mesh : Humans Child Sublingual Immunotherapy T-Lymphocytes, Regulatory / metabolism Rhinitis, Allergic / therapy Treatment Outcome Cytokines Allergens

来  源:   DOI:10.1007/s12325-024-02819-8

Abstract:
BACKGROUND: Allergen-specific immunotherapy (AIT) plays a pivotal role in altering the immune status and tissue responses in allergic rhinitis (AR). This study focuses on the impact of sublingual immunotherapy (SLIT) involving dust mite drops, exploring the modulation of regulatory T cells (Treg) and their specific marker, BLIMP1, in the nasal mucosa.
METHODS: Immune cells were isolated from nasal lavage fluid of patients with AR undergoing SLIT (n = 94). Treg cells were analyzed for BLIMP1 expression, and chemokine levels associated with Treg recruitment were assessed using Luminex assay. Patients were categorized on the basis of SLIT efficacy and followed for changes after discontinuation.
RESULTS: SLIT induced a significant increase in nasal Treg cells (7.09 ± 2.59% vs. 0.75 ± 0.27%, P < 0.0001). BLIMP1 expression in Treg cells notably increased after SLIT (0.36 ± 0.22% to 16.86 ± 5.74%, P < 0.0001). Ineffective SLIT cases exhibited lower levels of nasal Treg and Blimp1 + Treg cells (both P < 0.0001). Receiver operating characteristic (ROC) analysis confirmed their potential as efficacy predictors (AUC = 0.908 and 0.968, respectively). SLIT discontinuation led to a significant reduction in Treg and Blimp1 + Treg cells (P < 0.001), emphasizing their maintenance during treatment. Pro-inflammatory cytokines decreased (P < 0.001), while CCL2 associated with Treg recruitment increased (P = 0.0015).
CONCLUSIONS: Elevated nasal Blimp1 + Treg cells serve as a predictive biomarker for SLIT responsiveness in pediatric AR. Their influence on immunotherapy effectiveness contributes to a nuanced understanding of SLIT mechanisms, allowing for disease stratification and personalized treatment plans. This study offers scientific support for predicting SLIT efficacy, enhancing the prospects of improved treatment outcomes in AR.
摘要:
背景:变应原特异性免疫疗法(AIT)在改变变应性鼻炎(AR)的免疫状态和组织反应中起关键作用。这项研究的重点是涉及尘螨滴剂的舌下免疫疗法(SLIT)的影响,探索调节性T细胞(Treg)及其特异性标记的调节,BLIMP1,在鼻粘膜中。
方法:从接受SLIT的AR患者的鼻灌洗液中分离免疫细胞(n=94)。分析Treg细胞的BLIMP1表达,使用Luminex测定法评估与Treg募集相关的趋化因子水平。根据SLIT疗效对患者进行分类,并随访停药后的变化。
结果:SLIT诱导鼻Treg细胞显着增加(7.09±2.59%vs.0.75±0.27%,P<0.0001)。SLIT后Treg细胞BLIMP1表达显著增加(0.36±0.22%至16.86±5.74%,P<0.0001)。无效SLIT病例表现出较低水平的鼻Treg和Blimp1+Treg细胞(均P<0.0001)。接收器工作特性(ROC)分析证实了它们作为功效预测因子的潜力(分别为AUC=0.908和0.968)。SLIT停药导致Treg和Blimp1+Treg细胞显著减少(P<0.001),强调他们在治疗期间的维护。促炎细胞因子下降(P<0.001),而CCL2与Treg募集相关增加(P=0.0015)。
结论:升高的鼻Blimp1+Treg细胞可作为儿童ARSLIT反应性的预测生物标志物。它们对免疫治疗有效性的影响有助于对SLIT机制的细致理解。允许疾病分层和个性化治疗计划。这项研究为预测SLIT疗效提供了科学支持,提高AR治疗结局改善的前景。
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