关键词: Allergen immunotherapy T-cell response antibody asthma cockroach allergy nasal allergen challenge skin prick test transcriptome urban

来  源:   DOI:10.1016/j.jaci.2024.04.022

Abstract:
BACKGROUND: Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children.
OBJECTIVE: We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT.
METHODS: Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed.
RESULTS: Changes in mean NAC TNSS did not differ between SCIT-assigned (n = 28) versus placebo-assigned (n = 29) participants (P = .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P = .04). A 200-fold increase in cockroach serum-specific IgG4 was observed among subjects receiving SCIT (P < .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P = .002), while no effect was observed for IL-10 or IFN-γ.
CONCLUSIONS: A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG4 serum production and down-modulation of allergen-stimulated T-cell responses.
摘要:
背景:蟑螂过敏导致城市儿童哮喘发病。在这些高危儿童中,很少有试验涉及使用蟑螂过敏原进行皮下免疫疗法(SCIT)的效果。
目的:确定SCIT一年后对蟑螂过敏原的鼻过敏原攻击(NAC)反应是否会改善。
方法:城市哮喘儿童,蟑螂对NAC敏感和反应,参加了一项为期一年的使用德国蟑螂提取物的随机双盲安慰剂对照SCIT试验.主要终点是SCIT治疗12个月后NAC期间平均总鼻症状评分(TNSS)的变化。NAC期间鼻转录组反应的变化,皮肤点刺试验(SPT)风团大小,评估了血清过敏原特异性抗体产生和对蟑螂过敏原的T细胞反应.
结果:SCIT分配(n=28)与安慰剂分配(n=29)的参与者之间平均NACTNSS的变化没有差异(p=0.63)。与TNSS相关的鼻转录组反应,但未观察到治疗效果。两组蟑螂血清特异性IgE(sIgE)下降程度相似,而SCIT参与者中减少的蟑螂SPT风团大小更大(p=0.04)。在接受SCIT的受试者中观察到蟑螂sIgG4增加200倍(p<0.001),但在安慰剂组中没有变化。与安慰剂相比,SCIT中蟑螂过敏原刺激后的T细胞白介素-4反应下降幅度更大(p=0.002),而白细胞介素-10或干扰素-γ没有观察到效果。
结论:SCIT的一年未能改变NACTNSS和鼻转录组对蟑螂过敏原攻击的反应,尽管对过敏原特异性皮肤试验有系统影响,诱导血清sIgG4产生和下调过敏原刺激的T细胞应答。
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