Genetic and Environmental Contributions to Serological Biomarkers of Extracellular Matrix Remodeling in Asthma: A Twin Study

IF 4 2区医学 Q2 ALLERGY

Clinical and Translational Allergy Pub Date : 2025-08-04 DOI:10.1002/clt2.70089

Matej Andelic, Vibeke Backer, Kirsten Ohm Kyvik, Signe Holm Nielsen, Simon Francis Thomsen

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引用次数: 0

Abstract

Background

Asthma is characterized by airway obstruction driven by chronic inflammation, leading to extracellular matrix (ECM) remodeling. This involves ECM alterations, including increased collagen deposition and elastolysis, resulting in airway wall thickening and irreversible airflow limitation. Despite ECM remodeling's known role in asthma, no reliable tools track these changes, and the genetic and environmental factors driving them remain unclear.

Objective

This study investigated ECM remodeling in asthma by assessing 12 serological neo-epitopes related to collagen synthesis, degradation, and immune cell activity. Studying monozygotic (MZ) and dizygotic (DZ) twins, we explored genetic and environmental influences on ECM changes.

Methods

The study included 512 individuals from 256 twin pairs (89 MZ, 167 DZ), of which 200 were healthy and 312 had asthma. An exploratory panel of 12 ECM biomarkers reflecting type III and VI collagen formation (PRO-C3, PRO-C6), turnover (PRO-C4), degradation (C3M, C4M, C4Mα3, C6M, C7M), and immune cell activity (VICM, ELP-3, ELA-HNE, CC16-HNE) was measured in serum using ELISA.

Results

Asthma was linked to increased type IV collagen degradation (C4M). Airway obstruction showed decreased PRO-C6, C4Mα3, C6M, and C7M, while C4M and ELP-3 were elevated among twins. Classical twin analyses revealed genetic influence on multiple biomarkers, primarily C4Mα3, C7M, CC16-HNE, and VICM.

Conclusion

This study highlights ECM remodeling's role in asthma and airway obstruction, identifying distinct biomarker profiles. Genetic factors significantly influence ECM changes, suggesting potential genetic predispositions for ECM alterations and offering insights into asthma pathogenesis and future diagnostic and therapeutic strategies.

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遗传和环境对哮喘患者细胞外基质重塑的血清学生物标志物的影响：一项双胞胎研究

哮喘的特征是由慢性炎症引起的气道阻塞，导致细胞外基质（ECM）重塑。这涉及到ECM的改变，包括胶原沉积和弹性溶解增加，导致气道壁增厚和不可逆的气流限制。尽管已知ECM重塑在哮喘中的作用，但没有可靠的工具跟踪这些变化，并且驱动它们的遗传和环境因素仍不清楚。目的通过评估与胶原合成、降解和免疫细胞活性相关的12个血清学新表位，探讨哮喘中ECM的重塑。研究单卵双胞胎（MZ）和异卵双胞胎（DZ），我们探讨了遗传和环境对ECM变化的影响。方法对256对双胞胎（MZ 89对，DZ 167对）中的512人进行研究，其中健康200人，哮喘312人。采用ELISA法检测血清中反映III型和VI型胶原形成（PRO-C3、PRO-C6）、转化（PRO-C4）、降解（C3M、C4M、C4Mα3、C6M、C7M）和免疫细胞活性（VICM、ELP-3、ELA-HNE、CC16-HNE）的12种ECM生物标志物。结果哮喘与IV型胶原降解（C4M）增加有关。双胞胎气道阻塞表现为PRO-C6、C4Mα3、C6M、C7M降低，C4M、ELP-3升高。经典双生子分析揭示了遗传对多种生物标志物的影响，主要是C4Mα3、C7M、CC16-HNE和VICM。结论本研究强调了ECM重塑在哮喘和气道阻塞中的作用，确定了不同的生物标志物谱。遗传因素显著影响ECM改变，提示ECM改变的潜在遗传易感性，并为哮喘发病机制和未来的诊断和治疗策略提供见解。

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来源期刊

Clinical and Translational Allergy Immunology and Microbiology-Immunology

CiteScore

7.50

自引率

4.50%

发文量

117

审稿时长

12 weeks

期刊介绍： Clinical and Translational Allergy, one of several journals in the portfolio of the European Academy of Allergy and Clinical Immunology, provides a platform for the dissemination of allergy research and reviews, as well as EAACI position papers, task force reports and guidelines, amongst an international scientific audience. Clinical and Translational Allergy accepts clinical and translational research in the following areas and other related topics: asthma, rhinitis, rhinosinusitis, drug hypersensitivity, allergic conjunctivitis, allergic skin diseases, atopic eczema, urticaria, angioedema, venom hypersensitivity, anaphylaxis, food allergy, immunotherapy, immune modulators and biologics, animal models of allergic disease, immune mechanisms, or any other topic related to allergic disease.