Hiroyuki Tanaka1, Etsuro Yamaguchi1, Nobuhiro Asai2, Toyoharu Yokoi3, Masaki Nishimura1, Haruhisa Nakao4, Masashi Yoneda4, Yoshinori Ohtsuka5, Satoshi Konno6, Noritaka Yamada7. 1. Division of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Nagakute, Aichi, Japan. 2. Department of Infection Control and Prevention, School of Medicine, Aichi Medical University, Nagakute, Aichi, Japan. 3. Department of Pathology, Nagoya Ekisaikai Hospital, Nagoya, Aichi, Japan. 4. Division of Hepatology and Pancreatology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Nagakute, Aichi, Japan. 5. Department of Medicine, Hokkaido Chuo Rosai Hospita, Iwamizawa, Japan. 6. First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan. 7. Department of Respiratory Medicine, National Hospital Organization, Higashinagoya Hospital, Nagoya, Aichi, Japan.
Abstract
BACKGROUND: Development of reliable new biomarkers remains crucial to improve diagnosis and assessing disease activity in sarcoidosis. The objective of this study was to seek such markers from the gene expression signature of alveolar macrophages by transcriptome analysis. METHODS: Pooled RNA extracted from alveolar macrophages from patients with active sarcoidosis and control patients was subjected to transcriptome analysis using microarrays. Expressed gene intensity in sarcoidosis relative to that in control was calculated. We measured serum cathepsin S (CTSS) concentrations in 89 healthy volunteers, 107 patients with sarcoidosis, 26 with interstitial pneumonia, 150 with pneumoconiosis, and 76 with pulmonary mycobacteriosis by the enzyme-linked immunosorbent assay. RESULTS: Among 12 genes with ratios higher than that of a housekeeping gene, we selected CTSS for scrutinizing protein expression in serum because of the feasibility of the protein assay. CTSS concentrations were significantly increased in sarcoidosis compared with not only controls but also all the other lung diseases. Receiver operating characteristics curve for sarcoidosis and parenchymal lung diseases revealed an area under the curve of 0.800 (95% confidence interval, 0.751-0.850; p=1.4 x 10-18) with 70% sensitivity and 78% specificity at a CTSS concentration of 15.5 ng/ml. A significant trend was identified between CTSS concentrations and the number of affected organs. Serum CTSS concentrations varied in parallel with clinical courses both spontaneously and in response to corticosteroid therapy. Epithelioid cells in granulomas were positive for immunohistochemical staining with CTSS. CONCLUSIONS: CTSS has the potential to be a useful biomarker in sarcoidosis. Copyright:
BACKGROUND: Development of reliable new biomarkers remains crucial to improve diagnosis and assessing disease activity in sarcoidosis. The objective of this study was to seek such markers from the gene expression signature of alveolar macrophages by transcriptome analysis. METHODS: Pooled RNA extracted from alveolar macrophages from patients with active sarcoidosis and control patients was subjected to transcriptome analysis using microarrays. Expressed gene intensity in sarcoidosis relative to that in control was calculated. We measured serum cathepsin S (CTSS) concentrations in 89 healthy volunteers, 107 patients with sarcoidosis, 26 with interstitial pneumonia, 150 with pneumoconiosis, and 76 with pulmonary mycobacteriosis by the enzyme-linked immunosorbent assay. RESULTS: Among 12 genes with ratios higher than that of a housekeeping gene, we selected CTSS for scrutinizing protein expression in serum because of the feasibility of the protein assay. CTSS concentrations were significantly increased in sarcoidosis compared with not only controls but also all the other lung diseases. Receiver operating characteristics curve for sarcoidosis and parenchymal lung diseases revealed an area under the curve of 0.800 (95% confidence interval, 0.751-0.850; p=1.4 x 10-18) with 70% sensitivity and 78% specificity at a CTSS concentration of 15.5 ng/ml. A significant trend was identified between CTSS concentrations and the number of affected organs. Serum CTSS concentrations varied in parallel with clinical courses both spontaneously and in response to corticosteroid therapy. Epithelioid cells in granulomas were positive for immunohistochemical staining with CTSS. CONCLUSIONS: CTSS has the potential to be a useful biomarker in sarcoidosis. Copyright:
Authors: Robert Su; Michael M Li; Nirav R Bhakta; Owen D Solberg; Eli P B Darnell; Joris Ramstein; Suresh Garudadri; Melissa Ho; Prescott G Woodruff; Laura L Koth Journal: Eur Respir J Date: 2014-08-19 Impact factor: 16.671
Authors: Jan C Grutters; Jean-Marc Fellrath; Leontine Mulder; Rob Janssen; Jules M M van den Bosch; Heleen van Velzen-Blad Journal: Chest Date: 2003-07 Impact factor: 9.410