{"title":"作为抗 T2 哮喘生物标志物的 LTF mRNA 表达水平研究","authors":"","doi":"10.1016/j.jaci.2024.05.013","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Lactotransferrin (LTF) has an immunomodulatory function, and its expression levels are associated with asthma susceptibility.</p></div><div><h3>Objectives</h3><p>We sought to investigate LTF messenger RNA (mRNA) expression levels in human bronchial epithelial cells (BECs) as an anti–type 2 (T2) asthma biomarker.</p></div><div><h3>Methods</h3><p>Association analyses between LTF mRNA expression levels in BECs and asthma-related phenotypes were performed in the Severe Asthma Research Program (SARP) cross-sectional (n = 155) and longitudinal (n = 156) cohorts using a generalized linear model. Correlation analyses of mRNA expression levels between LTF and all other genes were performed by Spearman correlation.</p></div><div><h3>Results</h3><p>Low LTF mRNA expression levels were associated with asthma susceptibility and severity (<em>P</em> < .025), retrospective and prospective asthma exacerbations, and low lung function (<em>P</em> < 8.3 × 10<sup>−3</sup>). Low LTF mRNA expression levels were associated with high airway T2 inflammation biomarkers (sputum eosinophils and fractional exhaled nitric oxide; <em>P</em> < 8.3 × 10<sup>−3</sup>) but were not associated with blood eosinophils or total serum IgE. LTF mRNA expression levels were negatively correlated with expression levels of T<sub>H</sub>2 or asthma-associated genes (<em>POSTN, NOS2,</em> and <em>MUC5AC</em>) and eosinophil-related genes (<em>IL1RL1, CCL26,</em> and <em>IKZF2</em>) and positively correlated with expression levels of T<sub>H</sub>1 and inflammation genes (<em>IL12A, MUC5B,</em> and <em>CC16</em>) and T<sub>H</sub>17-driven cytokines or chemokines for neutrophils (<em>CXCL1, CXCL6,</em> and <em>CSF3</em>) (<em>P</em> < 3.5 × 10<sup>−6</sup>).</p></div><div><h3>Conclusions</h3><p>Low LTF mRNA expression levels in BECs are associated with asthma susceptibility, severity, and exacerbations through upregulation of airway T2 inflammation. LTF is a potential anti-T2 biomarker, and its expression levels may help determine the balance of eosinophilic and neutrophilic asthma.</p></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Investigation of lactotransferrin messenger RNA expression levels as an anti–type 2 asthma biomarker\",\"authors\":\"\",\"doi\":\"10.1016/j.jaci.2024.05.013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Lactotransferrin (LTF) has an immunomodulatory function, and its expression levels are associated with asthma susceptibility.</p></div><div><h3>Objectives</h3><p>We sought to investigate LTF messenger RNA (mRNA) expression levels in human bronchial epithelial cells (BECs) as an anti–type 2 (T2) asthma biomarker.</p></div><div><h3>Methods</h3><p>Association analyses between LTF mRNA expression levels in BECs and asthma-related phenotypes were performed in the Severe Asthma Research Program (SARP) cross-sectional (n = 155) and longitudinal (n = 156) cohorts using a generalized linear model. Correlation analyses of mRNA expression levels between LTF and all other genes were performed by Spearman correlation.</p></div><div><h3>Results</h3><p>Low LTF mRNA expression levels were associated with asthma susceptibility and severity (<em>P</em> < .025), retrospective and prospective asthma exacerbations, and low lung function (<em>P</em> < 8.3 × 10<sup>−3</sup>). Low LTF mRNA expression levels were associated with high airway T2 inflammation biomarkers (sputum eosinophils and fractional exhaled nitric oxide; <em>P</em> < 8.3 × 10<sup>−3</sup>) but were not associated with blood eosinophils or total serum IgE. LTF mRNA expression levels were negatively correlated with expression levels of T<sub>H</sub>2 or asthma-associated genes (<em>POSTN, NOS2,</em> and <em>MUC5AC</em>) and eosinophil-related genes (<em>IL1RL1, CCL26,</em> and <em>IKZF2</em>) and positively correlated with expression levels of T<sub>H</sub>1 and inflammation genes (<em>IL12A, MUC5B,</em> and <em>CC16</em>) and T<sub>H</sub>17-driven cytokines or chemokines for neutrophils (<em>CXCL1, CXCL6,</em> and <em>CSF3</em>) (<em>P</em> < 3.5 × 10<sup>−6</sup>).</p></div><div><h3>Conclusions</h3><p>Low LTF mRNA expression levels in BECs are associated with asthma susceptibility, severity, and exacerbations through upregulation of airway T2 inflammation. LTF is a potential anti-T2 biomarker, and its expression levels may help determine the balance of eosinophilic and neutrophilic asthma.</p></div>\",\"PeriodicalId\":14936,\"journal\":{\"name\":\"Journal of Allergy and Clinical Immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.4000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Allergy and Clinical Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0091674924005244\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Allergy and Clinical Immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0091674924005244","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
Investigation of lactotransferrin messenger RNA expression levels as an anti–type 2 asthma biomarker
Background
Lactotransferrin (LTF) has an immunomodulatory function, and its expression levels are associated with asthma susceptibility.
Objectives
We sought to investigate LTF messenger RNA (mRNA) expression levels in human bronchial epithelial cells (BECs) as an anti–type 2 (T2) asthma biomarker.
Methods
Association analyses between LTF mRNA expression levels in BECs and asthma-related phenotypes were performed in the Severe Asthma Research Program (SARP) cross-sectional (n = 155) and longitudinal (n = 156) cohorts using a generalized linear model. Correlation analyses of mRNA expression levels between LTF and all other genes were performed by Spearman correlation.
Results
Low LTF mRNA expression levels were associated with asthma susceptibility and severity (P < .025), retrospective and prospective asthma exacerbations, and low lung function (P < 8.3 × 10−3). Low LTF mRNA expression levels were associated with high airway T2 inflammation biomarkers (sputum eosinophils and fractional exhaled nitric oxide; P < 8.3 × 10−3) but were not associated with blood eosinophils or total serum IgE. LTF mRNA expression levels were negatively correlated with expression levels of TH2 or asthma-associated genes (POSTN, NOS2, and MUC5AC) and eosinophil-related genes (IL1RL1, CCL26, and IKZF2) and positively correlated with expression levels of TH1 and inflammation genes (IL12A, MUC5B, and CC16) and TH17-driven cytokines or chemokines for neutrophils (CXCL1, CXCL6, and CSF3) (P < 3.5 × 10−6).
Conclusions
Low LTF mRNA expression levels in BECs are associated with asthma susceptibility, severity, and exacerbations through upregulation of airway T2 inflammation. LTF is a potential anti-T2 biomarker, and its expression levels may help determine the balance of eosinophilic and neutrophilic asthma.
期刊介绍：
The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.
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