TY - JOUR
T1 - Investigation of lactotransferrin messenger RNA expression levels as an anti–type 2 asthma biomarker
AU - Li, Nicholas C.
AU - Iannuzo, Natalie
AU - Christenson, Stephanie A.
AU - Langlais, Paul R.
AU - Kraft, Monica
AU - Ledford, Julie G.
AU - Li, Xingnan
N1 - Publisher Copyright:
© 2024 American Academy of Allergy, Asthma & Immunology
PY - 2024/9
Y1 - 2024/9
N2 - 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.
AB - 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.
KW - Anti-T2 biomarker
KW - T2 inflammation
KW - asthma exacerbations
KW - asthma susceptibility
KW - bronchial epithelial cells
KW - eosinophils
KW - lactotransferrin
KW - mRNA expression
KW - neutrophils
KW - severe asthma
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U2 - 10.1016/j.jaci.2024.05.013
DO - 10.1016/j.jaci.2024.05.013
M3 - Article
C2 - 38797239
AN - SCOPUS:85195856938
SN - 0091-6749
VL - 154
SP - 609
EP - 618
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 3
ER -