Expression of S100A9 and KL-6 in common interstitial lung diseases

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 PaO 2 (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.

Calprotectin as a Possible Biomarker in Various Lung Diseases

“…However, S100A9 levels in BAL fluid were positively correlated with KL-6 expression and the percentage of neutrophils in IPF patients and negatively correlated with lung function parameters and oxygen levels in SAR patients. The study concludes that measuring both KL-6 and S100A9 levels in BAL fluid can be useful for differential diagnosis of the four ILDs [25].…”

“…The study suggests that ILD is independently associated with increased FC levels in SSc [24]. Lin et al, [25] investigated whether S100A9 and Klebs von den Lungen-6 (KL-6) can be used as biomarkers for the differential diagnosis and disease progression of four common interstitial lung diseases (ILDs): idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, connective tissue disease-associated ILD, and sarcoidosis (SAR). The study collected data from patients who underwent fiber-optic bronchoscopy and bronchoalveolar lavage (BAL) at a hospital in China between 2012 and 2020.…”

Characteristics of Interstitial Pneumonia With Autoimmune Features (IPAF): Protocol for a Multicenter Prospective Study

“…It has also been demonstrated that S1009A may promote atherosclerosis [ 36 ]. In an observational study by Lin et al [ 37 ], it was revealed that S100A9 levels were significantly elevated in BALF samples obtained from patients with severe IPF. It has also been demonstrated that S100A9 levels in the BALF of patients with IPF are positively correlated with the percentage of BALF neutrophils.…”

Phenotypes and Serum Biomarkers in Sarcoidosis

“…Krebs von den Lungen-6 (KL-6) is a mucin-1 glycoprotein encoded by the MUC1 gene [70]. It is normally expressed on type II pneumocytes in lung tissue.…”

“…Serum KL-6 is thought to be produced by regenerating type II epithelial cells, with levels correlating to disease activity [71]. KL-6 also functions as a cell-surface barrier and should play a protective role associated with damage to the alveolar epithelial barrier molecule [70]. Notably, KL-6 levels have been reported to exhibit an inverse correlation with DLCO [49].…”