组织蛋白酶S，一种通过肺泡巨噬细胞转录组分析发现的结节病新血清生物标志物。
Cathepsin S, a new serum biomarker of sarcoidosis discovered by transcriptome analysis of alveolar macrophages.
作者信息
Tanaka Hiroyuki, Yamaguchi Etsuro, Asai Nobuhiro, Yokoi Toyoharu, Nishimura Masaki, Nakao Haruhisa, Yoneda Masashi, Ohtsuka Yoshinori, Konno Satoshi, Yamada Noritaka
机构信息
Division of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Nagakute, Aichi, Japan.
Department of Infection Control and Prevention, School of Medicine, Aichi Medical University, Nagakute, Aichi, Japan.
出版信息
Sarcoidosis Vasc Diffuse Lung Dis. 2019;36(2):141-147. doi: 10.36141/svdld.v36i2.7620. Epub 2019 May 1.
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) 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.
背景
开发可靠的新型生物标志物对于改善结节病的诊断和评估疾病活动仍然至关重要。本研究的目的是通过转录组分析从肺泡巨噬细胞的基因表达特征中寻找此类标志物。
方法
从活动性结节病患者和对照患者的肺泡巨噬细胞中提取的混合RNA使用微阵列进行转录组分析。计算结节病中基因表达强度相对于对照中的表达强度。我们通过酶联免疫吸附测定法测量了89名健康志愿者、107名结节病患者、26名间质性肺炎患者、150名尘肺病患者和76名肺分枝杆菌病患者的血清组织蛋白酶S（CTSS）浓度。
结果
在12个比值高于管家基因的基因中，由于蛋白质检测的可行性，我们选择CTSS来仔细研究血清中的蛋白质表达。与对照组以及所有其他肺部疾病相比，结节病患者的CTSS浓度显著升高。结节病和实质性肺部疾病的受试者工作特征曲线显示，曲线下面积为0.800（95%置信区间，0.751 - 0.850；p = 1.4×10），在CTSS浓度为15.5 ng/ml时，敏感性为70%，特异性为78%。在CTSS浓度与受累器官数量之间发现了显著趋势。血清CTSS浓度在自发情况下以及对皮质类固醇治疗的反应中均与临床病程平行变化。肉芽肿中的上皮样细胞CTSS免疫组织化学染色呈阳性。
结论
CTSS有潜力成为结节病中一种有用的生物标志物。
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