Multiarray screening identifies plasma proteins associated with Th17 cell differentiation and viral defense in coincident asthma and obesity.

IF 4.3 2区医学 Q2 ALLERGY Pediatric Allergy and Immunology Pub Date : 2024-07-01 DOI:10.1111/pai.14187

Hannes Manell, Nikolaos Tsolakis, Christer Janson, Andrei Malinovschi, Kjell Alving

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Abstract

Background: The immunological mechanisms behind the clinical association between asthma and obesity in adolescence are not fully understood. This study aimed to find new plasma protein biomarkers associated specifically with coincident asthma and obesity in adolescents.

Methods: This was a cross-sectional study in children and adolescents 10-19 years old (N = 390). Relative plasma concentrations of 113 protein biomarkers related to inflammation and immune response were determined by proximity extension assay (Target 96; Olink, Uppsala, Sweden). Differences in protein concentrations between healthy controls (n = 84), subjects with asthma (n = 138), subjects with obesity (n = 107), and subjects with both asthma and obesity (AO; n = 58) were analyzed by ANCOVA, adjusting for age and sex, and in a separate model adjusting also for the sum of specific IgE antibody concentrations to a mix of food allergens (fx5) and aeroallergens (Phadiatop). Proteins elevated in the AO group but not in the obesity or asthma groups were considered specifically elevated in asthma and obesity.

Results: Five proteins were elevated specifically in the AO group compared to controls (here sorted from largest to smallest effect of asthma and obesity combined): CCL8, IL-33, IL-17C, FGF-23, and CLEC7A. The effects of adjusting also for specific IgE were small but IL-33, IL-17C, and FGF-23 were no longer statistically significant.

Conclusion: We identified several new potential plasma biomarkers specifically elevated in coincident asthma and obesity in adolescents. Four of the proteins, CCL8, IL-33, IL-17C, and CLEC7A, have previously been associated with viral mucosal host defense and Th17 cell differentiation.

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多阵列筛选确定了与哮喘和肥胖同时发生时 Th17 细胞分化和病毒防御相关的血浆蛋白。

背景：青少年哮喘与肥胖之间的临床关联背后的免疫学机制尚未完全明了。本研究旨在寻找与青少年同时患哮喘和肥胖症特别相关的新血浆蛋白生物标志物：这是一项横断面研究，研究对象为 10-19 岁的儿童和青少年（N = 390）。通过近距离延伸测定法（Target 96; Olink, Uppsala, Sweden）测定了113种与炎症和免疫反应有关的蛋白质生物标志物的相对血浆浓度。对健康对照组（n = 84）、哮喘患者（n = 138）、肥胖患者（n = 107）以及哮喘和肥胖患者（AO；n = 58）之间的蛋白质浓度差异进行了方差分析，并对年龄和性别进行了调整，还在一个单独的模型中对食物过敏原（fx5）和航空过敏原（Phadiatop）的特异性 IgE 抗体总和进行了调整。在 AO 组中升高而在肥胖或哮喘组中没有升高的蛋白质被认为是在哮喘和肥胖中特别升高的蛋白质：结果：与对照组相比，有五种蛋白质在 AO 组中特别升高（此处按哮喘和肥胖的综合影响从大到小排序）：CCL8、IL-33、IL-17C、FGF-23 和 CLEC7A。同时调整特异性 IgE 的影响较小，但 IL-33、IL-17C 和 FGF-23 不再具有统计学意义：结论：我们发现了几种新的潜在血浆生物标志物，这些标志物在青少年合并哮喘和肥胖时会特别升高。其中四种蛋白质（CCL8、IL-33、IL-17C 和 CLEC7A）以前曾与病毒粘膜宿主防御和 Th17 细胞分化有关。

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来源期刊

Pediatric Allergy and Immunology 医学-过敏

CiteScore

9.10

自引率

9.10%

发文量

200

审稿时长

4-8 weeks

期刊介绍： Pediatric Allergy and Immunology is the world''s leading journal in pediatric allergy, publishing original contributions and comprehensive reviews related to the understanding and treatment of immune deficiency and allergic inflammatory and infectious diseases in children. Other areas of interest include: development of specific and accessory immunity; the immunological interaction during pregnancy and lactation between mother and child. As Pediatric Allergy and Immunology promotes communication between scientists engaged in basic research and clinicians working with children, we publish both clinical and experimental work.