Masako Watanabe1, Yasushi Horimasu2, Hiroshi Iwamoto1, Kakuhiro Yamaguchi1, Shinjiro Sakamoto1, Takeshi Masuda1, Taku Nakashima1, Shintaro Miyamoto1, Shinichiro Ohshimo3, Kazunori Fujitaka1, Hironobu Hamada4, Nobuoki Kohno5, Noboru Hattori1. 1. Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan. 2. Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan, yasushi17@hiroshima-u.ac.jp. 3. Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan. 4. Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan. 5. Hiroshima Cosmopolitan University, Minami-ku, Hiroshima, Japan.
Abstract
BACKGROUND: Chronic hypersensitivity pneumonitis (CHP) is characterized by lymphocytic inflammation and progressive fibrosis of the lung caused by a variety of inhaled antigens. Due to the difficulty of accurately diagnosing CHP, and the poor prognosis associated with the condition, a novel clinical biomarker is urgently needed. OBJECTIVE: To investigate the usefulness of C-C motif chemokine ligand 15 (CCL15), which had been demonstrated to highly express in the lungs of CHP patients, as a clinical biomarker for CHP. METHOD: Immunohistochemical investigations were performed on lung tissue from CHP patients, and CCL15 levels in serum and bronchoalveolar lavage fluid (BALF) were measured via the enzyme-linked immunosorbent assay. RESULTS: Immunohistochemistry investigations revealed high CCL15 expression in the lungs of CHP patients. Serum CCL15 levels in CHP patients (29.1 ± 2.1 μg/mL) were significantly higher than those of idiopathic pulmonary fibrosis patients (19.7 ± 1.3 μg/mL, p = 0.01) and healthy subjects (19.5 ± 1.7 μg/mL, p = 0.003). When BALF CCL15 level was divided by BALF albumin (Alb) level (BALF CCL15/Alb), it was significantly inversely correlated with forced vital capacity (β = -0.47, p = 0.0006), percentage of predicted carbon monoxide diffusion capacity of the lung (β = -0.41, p = 0.0048), and BALF lymphocyte count (β = -0.34, p = 0.01) in CHP patients. Multivariate Cox proportional hazards analysis revealed that high BALF CCL15/Alb and poor prognosis were statistically significantly independently correlated in CHP patients (HR 1.1, 95% CI 1.03-1.18, p = 0.004). CONCLUSION: The results of the current study suggest that CCL15 may be a useful prognostic biomarker for CHP. CCL15 was highly expressed in the lung tissue of CHP patients, and BALF CCL15/Alb was significantly associated with CHP prognosis.
BACKGROUND:Chronic hypersensitivity pneumonitis (CHP) is characterized by lymphocytic inflammation and progressive fibrosis of the lung caused by a variety of inhaled antigens. Due to the difficulty of accurately diagnosing CHP, and the poor prognosis associated with the condition, a novel clinical biomarker is urgently needed. OBJECTIVE: To investigate the usefulness of C-C motif chemokine ligand 15 (CCL15), which had been demonstrated to highly express in the lungs of CHP patients, as a clinical biomarker for CHP. METHOD: Immunohistochemical investigations were performed on lung tissue from CHP patients, and CCL15 levels in serum and bronchoalveolar lavage fluid (BALF) were measured via the enzyme-linked immunosorbent assay. RESULTS: Immunohistochemistry investigations revealed high CCL15 expression in the lungs of CHP patients. Serum CCL15 levels in CHP patients (29.1 ± 2.1 μg/mL) were significantly higher than those of idiopathic pulmonary fibrosispatients (19.7 ± 1.3 μg/mL, p = 0.01) and healthy subjects (19.5 ± 1.7 μg/mL, p = 0.003). When BALF CCL15 level was divided by BALF albumin (Alb) level (BALF CCL15/Alb), it was significantly inversely correlated with forced vital capacity (β = -0.47, p = 0.0006), percentage of predicted carbon monoxide diffusion capacity of the lung (β = -0.41, p = 0.0048), and BALF lymphocyte count (β = -0.34, p = 0.01) in CHP patients. Multivariate Cox proportional hazards analysis revealed that high BALF CCL15/Alb and poor prognosis were statistically significantly independently correlated in CHP patients (HR 1.1, 95% CI 1.03-1.18, p = 0.004). CONCLUSION: The results of the current study suggest that CCL15 may be a useful prognostic biomarker for CHP. CCL15 was highly expressed in the lung tissue of CHP patients, and BALF CCL15/Alb was significantly associated with CHP prognosis.