Related Experiment Video
Updated: Sep 24, 2025
Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
Published on: September 20, 2024
Expression of S100A9 and KL-6 in common interstitial lung diseases
Li Lin1, Yabin Zhao1, Zhenhua Li1
1Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang, China.
Insights
Klebs von den Lungen-6 (KL-6) in bronchoalveolar lavage fluid can differentiate idiopathic pulmonary fibrosis from other interstitial lung diseases. S100 calcium binding protein A9 (S100A9) indicates sarcoidosis progression, suggesting combined use for ILD diagnosis.
Area of Science:
- Pulmonology and Respiratory Medicine
- Biomarker Discovery
- Immunology
Background:
- Interstitial lung diseases (ILDs) encompass a group of heterogeneous disorders with overlapping clinical and radiological features.
- Accurate differential diagnosis of ILDs is crucial for appropriate management and prognosis.
- S100 calcium binding protein A9 (S100A9) and Klebs von den Lungen-6 (KL-6) are potential biomarkers in respiratory diseases.
Purpose of the Study:
- To evaluate the utility of S100A9 and KL-6 as biomarkers for the differential diagnosis of four common ILDs.
- To investigate the correlation of S100A9 and KL-6 with disease progression and clinical parameters in ILDs.
- To assess the combined diagnostic value of S100A9 and KL-6 in differentiating ILDs.
Main Methods:
- Retrospective analysis of 98 patients diagnosed with idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, connective tissue disease-associated ILD, or sarcoidosis (SAR).
- Collection of clinical data, pulmonary function tests, bronchoalveolar lavage fluid (BALF) analysis, and serum/BALF S100A9 and KL-6 levels.
- Statistical analysis to compare biomarker levels between groups and correlate them with disease severity and progression.
Main Results:
- KL-6 levels in BALF were significantly higher in IPF patients compared to other ILDs (P < .05).
- S100A9 levels in BALF and serum did not significantly differ between the four ILD groups (P > .05).
- BALF S100A9 positively correlated with KL-6 and neutrophils in IPF; it increased with SAR stage, correlating negatively with lung function parameters.
Conclusions:
- BALF KL-6 is a valuable biomarker for differentiating IPF from other common ILDs.
- BALF S100A9 is useful for indicating sarcoidosis progression but not for differential diagnosis among the studied ILDs.
- Simultaneous measurement of BALF KL-6 and S100A9 enhances the differential diagnosis of common ILDs.
Abstract:
By evaluating S100 calcium binding protein A9 (S100A9) and Klebs von den Lungen-6 (KL-6) expression in patients with 4 common interstitial lung diseases (ILDs), we aimed to investigate whether S100A9 or KL-6 can be of any value in the differential diagnosis of these ILDs and simultaneously signal the disease progression.We collected the data of patients diagnosed with the 4 ILDs and underwent fiber-optic bronchoscopy and BAL in the First Affiliated Hospital, China Medical University from January 2012 to December 2020. The data related to BGA, C-reactive protein, pulmonary function test, total number and fraction of cells, T lymphocyte subsets in bronchoalveolar lavage fluid (BALF), and the expression of S100A9 and KL-6 in BALF and serum were collected. We analyzed, whether S100A9 or KL-6 could serve as a biomarker for differential diagnosis between the 4 common ILDs; whether the levels of S100A9 and KL-6 correlated with each other; whether they were correlated with other clinical parameters and disease severity.This study included 98 patients, 37 patients with idiopathic pulmonary fibrosis (IPF), 12 with hypersensitivity pneumonitis, 13 with connective tissue disease-associated ILD, and 36 with sarcoidosis (SAR): stage I (18), stage II (9), stage III (5), and stage IV (4). The expression of KL-6 in BALF was significantly higher in IPF patients than other 3 groups (all P-value < .05). However, there was no significant difference in the levels of S100A9 in BALF and serum between the 4 groups (P-value > .05). The levels of S100A9 in BALF of IPF patients was positively and significantly correlated with KL-6 expression and the percentage of neutrophils in BALF (P-value < .05). Along with the stage increase of SAR patients, the level of S100A9 in BALF gradually increased, which was negatively and significantly correlated with the forced vital capacity/predicted, carbon monoxide diffusing capacity/predicted%, and PaO2 (all P-value < .05).The expression of KL-6 in BALF can be used as a biomarker to differentiate IPF from the other 3 common ILDs. While, this was not the case with expression of S100A9 in BALF and serum. However, the expression S100A9 in BALF is useful to indicate the progression of SAR. Thus, simultaneous measurement of KL-6 and S100A9 levels in BALF makes more sense in differential diagnosing of the 4 common ILDS.
