Fang Heping, Li Juan, Li Xiangyu, Wen Xiang, Zeng Dan, Tang Yuyi, Wang Run, Zang Na, Zhong Wen, Ren Luo, Liu Enmei
Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Key Laboratory of Children's Important Organ Development and Diseases of Chongqing Municipal Health Commission, Chongqing, China.
Guangzhou National Laboratory, Guangzhou, China.
World Allergy Organ J. 2025 Aug 8;18(8):101097. doi: 10.1016/j.waojou.2025.101097. eCollection 2025 Aug.
Fungi play a significant role in promoting acute exacerbations and poor control of allergic asthma (AA), particularly in children. In Southwest China, characterized by a humid and warm climate, moderate year-round fungal pollution is closely associated with the onset of childhood asthma. Despite this, little is known about the characteristics of fungal allergens in asthmatic children in this region.
This study aimed to investigate fungal sensitization in children with AA and its association with AA features.
A cross-sectional study was conducted at a children's hospital in Southwest China, involving 281 AA children and 20 healthy controls. Specific IgE (sIgE) levels for 13 fungal species and 3 (SEs) were measured using microfluidic chips. Olink proteomics was used to analyze plasma samples from 46 AA children to explore molecular features associated with fungal sensitization.
The sensitization rate to fungi and SEs in AA children was 75.4% (compared to 30% in healthy controls), with (RN) showing the highest sensitization rate at 67.3% (0% in healthy children). RN-sIgE was significantly correlated with total IgE ( = 0.76), -sIgE ( = 0.67), -sIgE ( = 0.67), blood eosinophil count (BEC, = 0.26), fractional exhaled nitric oxide (FeNO, = 0.20), and Childhood Asthma Control Test (C-ACT, = -0.17). Proteomic analysis identified 61 upregulated plasma proteins in AA children with RN sensitization, including IL5RA, PRG2, PRSS2 and PRG3, forming a protein-protein interaction (PPI) network linked to innate immunity (53.1%) and proteolysis (21.9%). These proteins showed greater overlap with mycosis-associated proteins in the UK Biobank than with AA-associated proteins. A total IgE threshold of 395.0 kU/L statistically predicted RN sensitization with high accuracy (AUC 0.91) in this population. This was demonstrated in a case of refractory "nonallergic" asthma (negative for 19 common allergens) with an elevated total IgE level (461.4 IU/mL) and RN sensitization (0.72 IU/mL).
RN sensitization is relatively common in children with AA from Southwest China and may be associated with innate immune responses and proteolysis pathways. These findings suggest a possible underappreciation of RN's role in AA, warranting further investigation.
真菌在促进过敏性哮喘(AA)的急性加重和控制不佳方面起着重要作用,尤其是在儿童中。在中国西南部,气候湿润温暖,全年真菌污染程度适中,这与儿童哮喘的发病密切相关。尽管如此,关于该地区哮喘儿童真菌过敏原的特征知之甚少。
本研究旨在调查AA患儿的真菌致敏情况及其与AA特征的关联。
在中国西南部的一家儿童医院进行了一项横断面研究,纳入281名AA患儿和20名健康对照。使用微流控芯片测量13种真菌和3种霉菌的特异性IgE(sIgE)水平。采用Olink蛋白质组学技术分析46名AA患儿的血浆样本,以探索与真菌致敏相关的分子特征。
AA患儿对真菌和霉菌的致敏率为75.4%(健康对照为30%),其中烟曲霉(RN)的致敏率最高,为67.3%(健康儿童为0%)。RN-sIgE与总IgE(r = 0.76)、屋尘螨-sIgE(r = 0.67)、粉尘螨-sIgE(r = 0.67)、血嗜酸性粒细胞计数(BEC,r = 0.26)、呼出一氧化氮分数(FeNO,r = 0.20)和儿童哮喘控制测试(C-ACT,r = -0.17)显著相关。蛋白质组学分析确定了46名对RN致敏的AA患儿血浆中有61种上调蛋白,包括IL5RA、PRG2、PRSS2和PRG3,形成了一个与固有免疫(53.1%)和蛋白水解(21.9%)相关的蛋白质-蛋白质相互作用(PPI)网络。这些蛋白与英国生物银行中与真菌病相关的蛋白的重叠程度高于与AA相关的蛋白。在该人群中,总IgE阈值为395.0 kU/L时,对RN致敏具有较高的统计预测准确性(AUC 0.91)。在一例难治性“非过敏性”哮喘(19种常见过敏原均为阴性)中得到证实,其总IgE水平升高(461.4 IU/mL)且对RN致敏(0.72 IU/mL)。
在中国西南部的AA患儿中,RN致敏相对常见,可能与固有免疫反应和蛋白水解途径有关。这些发现表明RN在AA中的作用可能未得到充分认识,值得进一步研究。