Hironao Hozumi1,2, Tomoyuki Fujisawa3,4, Noriyuki Enomoto3,4, Ran Nakashima3,4, Yasunori Enomoto3,4, Yuzo Suzuki3,4, Masato Kono3,4, Masato Karayama3,4, Kazuki Furuhashi3,4, Akihiro Murakami3,4, Naoki Inui3,4, Yutaro Nakamura3,4, Tsuneyo Mimori3,4, Takafumi Suda3,4. 1. From the Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu; Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto; Department of IVD Development, Medical and Biological Laboratories Co. Ltd., Ina, Japan. jubilooreoresagi@yahoo.co.jp hozumi@hama-med.ac.jp. 2. H. Hozumi, MD, PhD, Research Associate, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; T. Fujisawa, MD, PhD, Research Associate, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Enomoto, MD, PhD, Lecturer, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; R. Nakashima, MD, PhD, Research Associate, Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University; Y. Enomoto, MD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Suzuki, MD, PhD, Research Associate, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Kono, MD, PhD, Research Associate, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Karayama, MD, PhD, Lecturer, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; K. Furuhashi, MD, PhD, Research Associate, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; A. Murakami, PhD, Department of IVD Development, Medical and Biological Laboratories Co. Ltd.; N. Inui, MD, PhD, Assistant Professor, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine; Y. Nakamura, MD, PhD, Lecturer, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; T. Mimori, MD, PhD, Professor, Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University; T. Suda, MD, PhD, Professor, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine. jubilooreoresagi@yahoo.co.jp hozumi@hama-med.ac.jp. 3. From the Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu; Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto; Department of IVD Development, Medical and Biological Laboratories Co. Ltd., Ina, Japan. 4. H. Hozumi, MD, PhD, Research Associate, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; T. Fujisawa, MD, PhD, Research Associate, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; N. Enomoto, MD, PhD, Lecturer, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; R. Nakashima, MD, PhD, Research Associate, Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University; Y. Enomoto, MD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; Y. Suzuki, MD, PhD, Research Associate, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Kono, MD, PhD, Research Associate, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; M. Karayama, MD, PhD, Lecturer, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; K. Furuhashi, MD, PhD, Research Associate, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; A. Murakami, PhD, Department of IVD Development, Medical and Biological Laboratories Co. Ltd.; N. Inui, MD, PhD, Assistant Professor, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine; Y. Nakamura, MD, PhD, Lecturer, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine; T. Mimori, MD, PhD, Professor, Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University; T. Suda, MD, PhD, Professor, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine.
Abstract
OBJECTIVE: Interstitial lung disease (ILD) is involved in polymyositis/dermatomyositis (PM/DM), a disease associated with poor prognoses. Chitinase-3-like-1 protein (YKL-40) has pleiotropic biological activities involved in inflammation, cell proliferation, and tissue remodeling; however, the clinical application of YKL-40 remains limited. We investigated the clinical significance of YKL-40 in PM/DM-ILD. METHODS: Sixty-nine consecutive patients with PM/DM-ILD and 34 healthy controls were analyzed. We measured baseline and followup serum YKL-40 using an ELISA, evaluated the association of YKL-40 with clinical variables and survival, and examined YKL-40 expression in lung specimens from patients with PM/DM-ILD using immunohistochemistry. RESULTS: Serum YKL-40 levels were significantly greater in patients with PM/DM-ILD compared with healthy controls (p < 0.0001). Serum YKL-40 was correlated with arterial oxygen pressure (r = -0.40, p < 0.001) and percent-predicted DLCO (r = -0.41, p = 0.01) in patients with PM/DM-ILD. Multivariate Cox hazard analysis demonstrated that higher serum YKL-40 and lower percent-predicted forced vital capacity were independently associated with a poor prognosis. Immunohistochemistry analysis demonstrated that YKL-40 expression was enhanced in aggregated intraalveolar macrophages and hyperproliferative alveolar epithelial cells in patients with PM/DM-ILD. CONCLUSION: YKL-40 is a promising biomarker for evaluating PM/DM-ILD activity/severity and predicting disease prognosis. Insights into YKL-40 might help elucidate the pathogenesis of PM/DM-ILD.
OBJECTIVE:Interstitial lung disease (ILD) is involved in polymyositis/dermatomyositis (PM/DM), a disease associated with poor prognoses. Chitinase-3-like-1 protein (YKL-40) has pleiotropic biological activities involved in inflammation, cell proliferation, and tissue remodeling; however, the clinical application of YKL-40 remains limited. We investigated the clinical significance of YKL-40 in PM/DM-ILD. METHODS: Sixty-nine consecutive patients with PM/DM-ILD and 34 healthy controls were analyzed. We measured baseline and followup serum YKL-40 using an ELISA, evaluated the association of YKL-40 with clinical variables and survival, and examined YKL-40 expression in lung specimens from patients with PM/DM-ILD using immunohistochemistry. RESULTS: Serum YKL-40 levels were significantly greater in patients with PM/DM-ILD compared with healthy controls (p < 0.0001). Serum YKL-40 was correlated with arterial oxygen pressure (r = -0.40, p < 0.001) and percent-predicted DLCO (r = -0.41, p = 0.01) in patients with PM/DM-ILD. Multivariate Cox hazard analysis demonstrated that higher serum YKL-40 and lower percent-predicted forced vital capacity were independently associated with a poor prognosis. Immunohistochemistry analysis demonstrated that YKL-40 expression was enhanced in aggregated intraalveolar macrophages and hyperproliferative alveolar epithelial cells in patients with PM/DM-ILD. CONCLUSION:YKL-40 is a promising biomarker for evaluating PM/DM-ILD activity/severity and predicting disease prognosis. Insights into YKL-40 might help elucidate the pathogenesis of PM/DM-ILD.
Authors: Shehabaldin Alqalyoobi; Ayodeji Adegunsoye; Angela Linderholm; Cara Hrusch; Claire Cutting; Shwu-Fan Ma; Anne Sperling; Imre Noth; Mary E Strek; Justin M Oldham Journal: Am J Respir Crit Care Med Date: 2020-01-15 Impact factor: 21.405