Krebs von den lungen-6 as a clinical marker for hypersensitivity pneumonitis: A meta-analysis and bioinformatics analysis

Abstract

AimHypersensitivity pneumonitis (HP), also referred to as exogenous allergic alveolitis, is one of the most common interstitial lung diseases (ILDs). A potential immune biomarker, Krebs von den lgen-6 (KL-6) characterizes the progression and severity of HP. The meta-analysis in this study was conducted to elucidate the variations in the concentrations of KL-6 in different types of HP.MethodsA systematic search of various databases such as EMBASE, Pubmed, CNKI, VIP, Web of Science, and WanFang was carried out to find relevant published articles between January 1980 and August 2022 that explored the relationship between KL-6 and allergic pneumonia. Standardized mean difference (SMD) and 95% confidence interval (CI) were used as effect sizes for comparison among different groups. The GSE47460 and GSE150910 datasets were downloaded to extract and validate the differences in KL-6 mRNA expression between HP lung tissue and healthy controls. Furthermore, the single-cell sequencing dataset GSE135893 was downloaded to extract KL-6 mRNA expression in type II alveolar epithelial cells to validate the differences between HP and healthy controls. Two researchers evaluated the quality of the included studies by employing Newcastle-Ottawa Scale. All the qualified studies were subjected to statistical analyses carried out utilizing RevMan 5.2, Stata 11.0, and R software 4.1.3.ResultsTwenty studies aligned perfectly with the inclusion criteria of the meta. The concentrations of KL-6 were substantially higher in the blood of HP patients as compared to the control group. Subgroup analyses were carried out in accordance with the allergen source and the results revealed that patients with different allergens had higher blood KL-6 concentrations than healthy controls. Additionally, different subgroups of subjects were created for meta-analysis as per the fibrosis status, race, measurement method, and sample type. The concentration of KL-6 in blood was much higher in all HP subgroups than in healthy control groups. Moreover, the bioinformatics analysis revealed that KL-6 mRNA expression was higher in HP lung tissue and type II alveolar epithelial cells as compared to healthy controls.ConclusionThe present meta-analysis and bioinformatics analysis suggested that the concentration levels of KL-6 varied between HP patients and healthy individuals, and the KL-6 concentrations may be higher in the blood samples of HP patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, CRD42022355334.

Targeting Progression in Pulmonary Fibrosis: An Overview of Underlying Mechanisms, Molecular Biomarkers, and Therapeutic Intervention

“…Moreover, the concentrations of serum KL-6 displayed a negative association with TLC and DLCO [66]. Based on a large meta-analysis [109], HP patients have a higher expression of KL-6 compared to normal individuals, with a substantial increase in patients with fibrotic HP. Elevated KL-6 concentrations were found to be closely linked to the progression of ILD as well as a substantial functional decline.…”

Acute Exacerbations of Interstitial Lung Diseases: Focus on Biomarkers

“…KL-6 levels have been reported to be increased in patients with HP compared to healthy individuals and could differentiate HP from IPF [ 133 ]. However, it remains unclear whether fibrotic or non-fibrotic HP exhibit higher levels of KL-6 [ 134 ]. In the study by Okamoto et al, KL-6 levels were not only higher in patients with chronic HP but also increased significantly during acute exacerbations of the disease [ 135 ].…”

Serum KL-6 and the mortality of patients with connective tissue disease-associated interstitial lung disease: A meta-analysis

“…Krebs von den Lungen-6 (KL-6) is a high-molecular-weight glycoprotein encoded by the MUC1 gene, primarily located on the cell surface of type II alveolar epithelial cells and bronchial epithelial cells (10). Elevated serum levels of KL-6 have been identified as a biomarker for alveolar epithelial proliferation and injury in various respiratory conditions (10), including acute respiratory distress syndrome (11), hypersensitivity pneumonia (12), idiopathic interstitial pneumonia (13), pulmonary sarcoidosis (14), coronavirus disease 2019 (COVID-19) (15), and CTD-ILD (16). Furthermore, several studies have indicated the potential predictive value of serum KL-6 in determining the prognosis of individuals with severe lung conditions, including idiopathic pulmonary fibrosis (17) and COVID-19 (18).…”