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骨膜蛋白是类风湿关节炎相关间质性肺疾病的生物标志物。

Periostin Is a Biomarker of Rheumatoid Arthritis-Associated Interstitial Lung Disease.

作者信息

Matama Goushi, Okamoto Masaki, Fujimoto Kiminori, Johkoh Takeshi, Tominaga Masaki, Mukae Hiroshi, Sakamoto Noriho, Komiya Kosaku, Umeki Kenji, Komatsu Masamichi, Shimizu Yasuo, Takahashi Koichiro, Tokisawa Saeko, Zaizen Yoshiaki, Matsuo Norikazu, Nouno Takashi, Kaieda Shinjiro, Ida Hiroaki, Izuhara Kenji, Hoshino Tomoaki

机构信息

Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Ashahi-Machi 67, Kurume 830-0011, Japan.

Department of Respirology and Clinical Research Center, National Hospital Organization Kyushu Medical Center, Jigyohama 1-8-1, Chuou-ku, Fukuoka 810-0065, Japan.

出版信息

J Clin Med. 2023 Nov 15;12(22):7100. doi: 10.3390/jcm12227100.

Abstract

Periostin was investigated as a biomarker for rheumatoid arthritis-associated interstitial lung disease (RA-ILD). This prospective study measured serum monomeric and total periostin, Klebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and lactate dehydrogenase (LDH) in 19 patients with RA-ILD, 20 RA without ILD, and 137 healthy controls (HC). All biomarkers were higher in RA-ILD than HC or RA without ILD. KL-6 accurately detected ILD in RA patients (area under curve [AUC] = 0.939) and moderately detected SP-D and monomeric and total periostin (AUC = 0.803, =0.767, =0.767, respectively). Monomeric and total periostin were negatively correlated with normal lung area and positively correlated with honeycombing, reticulation, fibrosis score, and the traction bronchiectasis grade but not inflammatory areas. Serum levels of SP-D, KL-6, and LDH did not correlate with the extent of those fibrotic areas on high-resolution CT. Serum monomeric and total periostin were higher in patients with RA-ILD with definite usual interstitial pneumonia pattern compared with other ILD patterns. Immunohistochemical analyses of biopsy or autopsy lung tissues from RA-ILD during the chronic phase and acute exacerbation showed that periostin was expressed in fibroblastic foci but not inflammatory or dense fibrosis lesions. Periostin is a potential biomarker for diagnosis, evaluating fibrosis, and deciding therapeutic strategies for patients with RA-ILD.

摘要

骨膜蛋白被作为类风湿关节炎相关间质性肺病(RA-ILD)的一种生物标志物进行研究。这项前瞻性研究检测了19例RA-ILD患者、20例无ILD的RA患者及137名健康对照(HC)的血清单体骨膜蛋白、总骨膜蛋白、克雷伯斯6型肺抗原(KL-6)、表面活性蛋白D(SP-D)和乳酸脱氢酶(LDH)。所有生物标志物在RA-ILD患者中均高于HC或无ILD的RA患者。KL-6能准确检测出RA患者中的ILD(曲线下面积[AUC]=0.939),对SP-D以及单体和总骨膜蛋白有中度检测能力(AUC分别为0.803、0.767、0.767)。单体和总骨膜蛋白与正常肺面积呈负相关,与蜂窝状改变、网状改变、纤维化评分及牵拉性支气管扩张分级呈正相关,但与炎症区域无关。SP-D、KL-6和LDH的血清水平与高分辨率CT上那些纤维化区域的范围无关。与其他ILD模式相比,具有明确的普通型间质性肺炎模式的RA-ILD患者血清单体和总骨膜蛋白水平更高。对RA-ILD患者慢性期和急性加重期的活检或尸检肺组织进行免疫组织化学分析显示,骨膜蛋白在成纤维细胞灶中表达,但在炎症或致密纤维化病变中不表达。骨膜蛋白是RA-ILD患者诊断、评估纤维化及制定治疗策略的一种潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6064/10672657/09fc52474ed2/jcm-12-07100-g001.jpg

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