S100A9 in BALF is a candidate biomarker of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, and the prognosis remains poor. On the other hand, other fibrotic interstitial pneumonias such as idiopathic nonspecific interstitial pneumonia (I-NSIP) and collagen vascular disease-associated interstitial pneumonia (CVD-IP) resemble IPF, but they respond to therapy and the prognosis is better. We searched for biomarkers to distinguish IPF from other fibrotic interstitial pneumonias and investigated whether S100A9 could be useful for discriminating types of fibrotic interstitial pneumonia based on our preliminary proteomic findings. We measured S100A9 levels in serum and bronchoalveolar lavage fluid (BALF) from 28 patients with IPF, 15 with I-NSIP, 20 with cryptogenic organizing pneumonia (COP), 35 with CVD-IP and 23 healthy individuals (controls) using enzyme-linked immunosorbent assays. S100A9 in the lung was also immunohistochemically localized. S100A9 levels in BALF, but not in serum, were significantly elevated in patients with IPF compared with I-NSIP, COP, CVD-IP and healthy individuals. S100A9 immunoreactivity was localized mainly in macrophages and neutrophils in lung specimens from patients with IPF. The results of receiver operating characteristic (ROC) curve analysis showed that BALF S100A9 levels had sufficient specificity and sensitivity to distinguish IPF from I-NSIP and CVD-IP. S100A9 in BALF might serve as a candidate biomarker to discriminate between IPF and other fibrotic interstitial pneumonias.

Hara A ，Sakamoto N ，Ishimatsu Y ，Kakugawa T ，Nakashima S ，Hara S ，Adachi M ，Fujita H ，Mukae H ，Kohno S ... -  《-》

Comparison of BALF concentrations of ENA-78 and IP10 in patients with idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia.

Nakayama S ，Mukae H ，Ishii H ，Kakugawa T ，Sugiyama K ，Sakamoto N ，Fujii T ，Kadota J ，Kohno S ... -  《RESPIRATORY MEDICINE》

High serum concentrations of autoantibodies to HSP47 in nonspecific interstitial pneumonia compared with idiopathic pulmonary fibrosis.

Kakugawa T ，Yokota S ，Mukae H ，Kubota H ，Sakamoto N ，Mizunoe S ，Matsuoka Y ，Kadota J ，Fujii N ，Nagata K ，Kohno S ... -  《BMC Pulmonary Medicine》

CCL18 in serum, BAL fluid and alveolar macrophage culture supernatant in interstitial lung diseases.

CCL18 is a CC chemokine produced mainly by antigen-presenting cells, and is chemotactic predominantly for T-lymphocytes. CCL18 can stimulate pulmonary fibroblasts and increase the collagen production in vitro. This study aimed to compare the CCL18 levels in a variety of human biological fluids between various interstitial lung diseases (ILDs), and to reveal potential correlations with BAL cell differentials. Serum and bronchoalveolar lavage fluid (BALF) samples were collected from 199 patients with idiopathic pulmonary fibrosis (IPF), idiopathic non-specific interstitial pneumonia (iNSIP), respiratory bronchiolitis interstitial lung disease/desquamative interstitial pneumonia (RB-ILD/DIP), cryptogenic organizing pneumonia (COP), hypersensitivity pneumonitis (HP) or sarcoidosis. Alveolar macrophage (AM) culture was performed in 44 patients with IPF, iNSIP, COP, HP, sarcoidosis or non-ILDs. The CCL18 levels in serum, BALF and AM culture supernatant were measured with ELISA. Both serum and BALF CCL18 levels in all ILDs were higher than in controls (all p < 0.005). In HP, CCL18 serum levels were the highest of all ILDs, and its BALF levels were significantly higher than in other ILDs except iNSIP. The BALF CCL18 levels markedly correlated with BAL cell differentials, especially with the percentage of BAL lymphocytes. In AM culture supernatant, the spontaneous CCL18 production was higher in HP and COP than in IPF and controls. CCL18 levels in serum, BALF and AM culture supernatant are markedly increased in various inflammatory and fibrotic ILDs. However, the CCL18 level being highest in HP among the investigated ILDs suggests that CCL18 may be more profoundly involved in inflammatory immune responses.

Cai M ，Bonella F ，He X ，Sixt SU ，Sarria R ，Guzman J ，Costabel U ... -  《-》

Elevated matrilysin levels in bronchoalveolar lavage fluid do not distinguish idiopathic pulmonary fibrosis from other interstitial lung diseases.

Vuorinen K ，Myllärniemi M ，Lammi L ，Piirilä P ，Rytilä P ，Salmenkivi K ，Kinnula VL ... -  《APMIS》