Specjalski Krzysztof, Romantowski Jan, Niedoszytko Marek
Department of Allergology, Medical University of Gdańsk, Gdańsk, Poland.
Front Med (Lausanne). 2023 Feb 8;10:1115938. doi: 10.3389/fmed.2023.1115938. eCollection 2023.
Asthma is a heterogeneous chronic disorder of the airways, with inflammation and bronchial hyperresponsiveness as its major underlying phenomena. Asthmatics vary in terms of inflammation pattern, concomitant pathologies, and factors aggravating the course of the disease. As a result, there is a need for sensitive and specific biomarkers that could facilitate diagnosing asthma as well as phenotyping in everyday practice. Chitinases and chitinase-like proteins (CLPs) seem promising in this field. Chitinases are evolutionarily conserved hydrolases that degrade chitin. In contrast, CLPs bind chitin but do not have degrading activity. Mammalian chitinases and CLPs are produced by neutrophils, monocytes, and macrophages in response to parasitic or fungal infections. Recently, several questions have been raised about their role in chronic airway inflammation. Several studies demonstrated that overexpression of CLP YKL-40 was associated with asthma. Moreover, it correlated with exacerbation rate, therapy resistance, poor control of symptoms, and, inversely, with FEV. YKL-40 facilitated allergen sensitization and IgE production. Its concentration was elevated in bronchoalveolar lavage fluid after an allergen challenge. It was also found to promote the proliferation of bronchial smooth muscle cells and correlate with subepithelial membrane thickness. Thus, it may be involved in bronchial remodeling. Associations between YKL-40 and particular asthma phenotypes remain unclear. Some studies showed that YKL-40 correlates with blood eosinophilia and FeNO, suggesting a role in T2-high inflammation. Quite the opposite, cluster analyses revealed the highest upregulation in severe neutrophilic asthma and obesity-associated asthma. The main limitation in the practical application of YKL-40 as a biomarker is its low specificity. High serum levels of YKL-40 were also found in COPD and several malignancies, in addition to infectious and autoimmune diseases. To conclude, the level of YKL-40 correlates with asthma and some clinical features in the whole asthmatic population. The highest levels are found in neutrophilic and obesity-related phenotypes. However, due to its low specificity, the practical application of YKL-40 remains uncertain but could be useful in phenotyping, especially when combined with other biomarkers.
哮喘是一种气道的异质性慢性疾病，炎症和支气管高反应性是其主要潜在现象。哮喘患者在炎症模式、伴随的病理状况以及加重疾病进程的因素方面存在差异。因此，需要敏感且特异的生物标志物，以在日常实践中便于哮喘的诊断和表型分析。几丁质酶和几丁质酶样蛋白（CLPs）在这一领域似乎很有前景。几丁质酶是进化上保守的水解酶，可降解几丁质。相比之下，CLPs可结合几丁质但不具有降解活性。哺乳动物的几丁质酶和CLPs由中性粒细胞、单核细胞和巨噬细胞在应对寄生虫或真菌感染时产生。最近，人们对它们在慢性气道炎症中的作用提出了一些疑问。多项研究表明，CLP YKL-40的过表达与哮喘有关。此外，它与疾病加重率、治疗抵抗、症状控制不佳呈正相关，与第一秒用力呼气容积（FEV）呈负相关。YKL-40促进变应原致敏和IgE产生。变应原激发后，其在支气管肺泡灌洗液中的浓度升高。还发现它可促进支气管平滑肌细胞的增殖，并与上皮下膜厚度相关。因此，它可能参与支气管重塑。YKL-40与特定哮喘表型之间的关联仍不明确。一些研究表明，YKL-40与血液嗜酸性粒细胞增多和呼出一氧化氮（FeNO）相关联，提示其在2型高炎症中起作用。恰恰相反，聚类分析显示在严重嗜中性粒细胞性哮喘和肥胖相关性哮喘中其上调程度最高。YKL-40作为生物标志物实际应用中的主要局限在于其特异性较低。除了感染性和自身免疫性疾病外，慢性阻塞性肺疾病（COPD）和几种恶性肿瘤中也发现血清YKL-40水平较高。总之，YKL-40水平与整个哮喘人群中的哮喘及一些临床特征相关。在嗜中性粒细胞性和肥胖相关表型中发现其水平最高。然而，由于其特异性较低，YKL-40的实际应用仍不确定，但在表型分析中可能有用，尤其是与其他生物标志物联合使用时。
