通过多克隆细胞因子鉴别年轻成年人的哮喘表型
2014/07/15
摘要
背景:最近的研究强调需要更好地鉴别哮喘表型,并在流行病学和临床研究中考虑潜在机制的类型。虽然过敏性哮喘和非过敏性哮喘在观察性研究和临床试验中常合并为1个病种,很少有研究调查这2个单独的表型与有代表性的年轻成年人的不同的细胞因子免疫档案的相关程度。
目的:探讨细胞因子基于产生的类型,这些类型是基于人群的出生队列研究中评价为年轻成年的过敏和过敏性哮喘患者的临床表型的基础。
方法:研究纳入底特律郊区的出生队列研究(儿童过敏性研究)的18 - 21岁参与者(N = 540)。研究结果为参与者对佛波醇酯刺激的全血白细胞介素(IL)-4、IL-5、IL-13、IL-10、IL-12、IL-17A、IL-17F、IL-22和干扰素-γ分泌反应的相关性。研究对过敏和非过敏性哮喘表型参与者与无哮喘参与者的研究结果进行了分析比较。
结果:辅助性T细胞(TH)2-极化反应[检测表现为更高的平均IL-5和IL-13分泌和更低比例的干扰素-γ和IL-12与3种TH2型细胞因子(IL-4、IL-5或IL-13)]只在过敏性哮喘参与者中观察到。与过敏性哮喘参与者相比,非过敏性哮喘与包括更高的调节干扰素γ分泌在内的TH1极化反应相关,令人惊讶的是,那些没有哮喘的参与者也是如此(比值比2.5,置信区间1.2-5.1,P<0.01)。
结论:正如预期的那样,具有过敏性哮喘表型史的年轻成年人在多克隆刺激后表现出TH2极化因子反应。然而,非过敏性哮喘史患者出现TH1极化反应。过敏和非过敏性哮喘与病因性的不同免疫类型相关,强调在分析研究和临床管理中区分这些类型的重要性。
(苏楠 审校)
AnnAllergyAsthmaImmunol.2014May3.pii:S1081-1206(14)00262-2.doi:10.1016/j.anai.2014.04.013. [Epub ahead of print]
Differentiating asthma phenotypes in young adults through polyclonal cytokine profiles.
Zoratti E1, Havstad S2, Wegienka G2, Nicholas C2, Bobbitt KR2, Woodcroft KJ2, Ownby DR3, Johnson CC2.
ABSTRACT
BACKGROUND: Recent research has emphasized the need to better discriminate asthma phenotypes and consider underlying mechanistic endotypes in epidemiologic and clinical studies. Although allergic asthma and nonallergic asthma are frequently combined into 1 disease category in observational research and clinical trials, few studies have investigated the extent to which these 2 separate phenotypes are associated with distinct cytokine immunologic profiles in a representative young adult population.
OBJECTIVE: To investigate the cytokine production-based endotypes underlying the clinical phenotypes of allergic and nonallergic asthma in a population-based birth cohort evaluated as young adults.
METHODS: Participants included 18- to 21-year-old members (n = 540) of a suburban Detroit birth cohort study, the Childhood Allergy Study. Phorbolmyristate acetate-stimulated whole blood interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, IL-17A, IL-17F, IL-22, and interferon-γ secretory responses were analyzed for associations comparing participants with allergic vsnonallergic asthma phenotypes with those without asthma.
RESULTS: T-helper cell type (TH) 2-polarized responses, measured as higher mean IL-5 and IL-13 secretions and lower ratios of interferon-γ and IL-12 to 3 TH2 cytokines (IL-4, IL-5, or IL-13), were observed only in participants with allergic asthma. Nonallergic asthma was associated with TH1-polarized responses, including higher adjusted interferon-γ secretion compared with participants with allergic asthma and, surprisingly, those without asthma (odds ratio 2.5, confidence interval 1.2-5.1, P < .01).
CONCLUSION: As expected, young adults with a history of an allergic asthma phenotype exhibited a TH2-polarized cytokine response after polyclonal stimulation. However, TH1 polarization was observed in patients with a history of nonallergic asthma. Allergic and nonallergic asthma are associated with etiologically distinct immune endotypes, underscoring the importance of discriminating these endotypes in research analyses and clinical management.
AnnAllergyAsthmaImmunol.2014May3.pii:S1081-1206(14)00262-2.doi:10.1016/j.anai.2014.04.013. [Epub ahead of print]
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儿童ω-3脂肪酸和哮喘的关系
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通过机器人(PIPER)采样提高暴露特征与儿童呼吸道症状、哮喘和湿疹的关系