Eosinophil extracellular traps in asthma: implications for pathogenesis and therapy

Shen, Kunlu; Zhang, Mengyuan; Zhao, Ruiheng; Li, Yun; Li, Chunxiao; Hou, Xin; Sun, Bingqing; Liu, Bowen; Xiang, Min; Lin, Jiangtao

doi:10.1186/s12931-023-02504-4

Cited by 5 publications

(2 citation statements)

References 134 publications

(184 reference statements)

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“…Sp-IgG has been found to directly trigger eosinophil extracellular trap cell death (EETosis) ( 8 ). EETosis causes damage to the airway epithelium by releasing potent eosinophilic inflammatory mediators ( 49 ). The persistent inflammation can create a feedback loop, where inflammatory cytokines and other mediators continuously activate B cells, leading to sustained production of Sp-IgG and ongoing tissue damage.…”

Section: Discussionmentioning

confidence: 99%

Presence of sputum IgG against eosinophilic inflammatory proteins in asthma

Qin,

Long,

Zhang

et al. 2024

Front. Immunol.

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BackgroundSputum immunoglobulin G (Sp-IgG) has been discovered to induce cytolytic extracellular trap cell death in eosinophils, suggesting a potential autoimmune mechanism contributing to asthma. This study aimed to explore the potential origin of Sp-IgG and identify clinically relevant subtypes of Sp-IgG that may indicate autoimmune events in asthma.MethodsThis study included 165 asthmatic patients and 38 healthy volunteers. We measured Sp-IgG and its five subtypes against eosinophil inflammatory proteins (Sp-IgGEPs), including eosinophil peroxidase, eosinophil major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and Charcot-Leyden Crystal protein in varying asthma severity. Clinical and Mendelian randomization (MR) analyses were conducted. A positive Sp-IgGEPs signature (Sp-IgGEPs+) was defined when any of the five Sp-IgGEPs values exceeded the predefined cutoff thresholds, calculated as the mean values of healthy controls plus twice the standard deviation.ResultsThe levels of Sp-IgG and Sp-IgGEPs were significantly elevated in moderate/severe asthma than those in mild asthma/healthy groups (all p < 0.05). Sp-IgG levels were positively correlated with airway eosinophil and Sp-IgGEPs. MR analysis showed causality between eosinophil and IgG (OR = 1.02, 95%CI = 1.00-1.04, p = 0.020), and elevated IgG was a risk factor for asthma (OR = 2.05, 95%CI = 1.00-4.17, p = 0.049). Subjects with Sp-IgGEPs+ exhibited worse disease severity and served as an independent risk factor contributing to severe asthma (adjusted-OR = 5.818, adjusted-95% CI = 2.193-15.431, adjusted-p < 0.001). Receiver operating characteristic curve analysis demonstrated that the combination of Sp-IgGEPs+ with non-allergic status, an ACT score < 15, and age ≥ 45 years, effectively predicted severe asthma (AUC = 0.84, sensitivity = 86.20%, specificity = 67.80%).ConclusionThis study identifies a significant association between airway eosinophilic inflammation, Sp-IgG, and asthma severity. The Sp-IgGEPs panel potentially serves as the specific biomarker reflecting airway autoimmune events in asthma.

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Section: Discussionmentioning

confidence: 99%

Presence of sputum IgG against eosinophilic inflammatory proteins in asthma

Qin,

Long,

Zhang

et al. 2024

Front. Immunol.

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“…In addition to neutrophils, other cell types including macrophages [33][34][35], eosinophils [36,37] and mast cells [38,39] may also produce extracellular traps. The function of these extracellular traps has not been well defined, but they are likely to have an important role in the host immune response.…”

Section: Bacteriamentioning

confidence: 99%

Neutrophil Extracellular Traps and Respiratory Disease

King,

Dousha

2024

JCM

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Extracellular traps made by neutrophils (NETs) and other leukocytes such as macrophages and eosinophils have a key role in the initial immune response to infection but are highly inflammatory and may contribute to tissue damage. They are particularly relevant to lung disease, with the pulmonary anatomy facilitating their ability to fully extend into the airways/alveolar space. There has been a rapid expansion in the number of published studies demonstrating their role in a variety of important respiratory diseases including chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis, asthma, pneumonia, COVID-19, rhinosinusitis, interstitial lung disease and lung cancer. The expression of NETs and other traps is a specific process, and diagnostic tests need to differentiate them from other inflammatory pathways/causes of cell death that are also characterised by the presence of extracellular DNA. The specific targeting of this pathway by relevant therapeutics may have significant clinical benefit; however, current clinical trials/evidence are at a very early stage. This review will provide a broad overview of the role of NETs and their possible treatment in respiratory disease.

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