Ye Lifang, Zuo Yu, Chen Fang, Xu Yuetong, Zhang Puli, Yang Hongxia, Lin Sang, Peng Qinglin, Wang Guochun, Shu Xiaoming
Department of Rheumatology, Key Laboratory of Myositis, China-Japan Friendship Hospital, Beijing, China.
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Front Med (Lausanne). 2022 May 3;9:903887. doi: 10.3389/fmed.2022.903887. eCollection 2022.
In the current study, we aimed to assess resistin mRNA levels in the peripheral blood mononuclear cells (PBMCs) of dermatomyositis patients with interstitial lung disease (DM-ILD) and their correlation with disease activity.
We detected resistin mRNA levels in the PBMCs of 37 DM-ILD, 8 DM patients without ILD, and 19 healthy control (HC) subjects by performing quantitative reverse transcription real-time polymerase chain reaction analysis. Associations between resistin expression levels and major clinical manifestations, laboratory examinations, and disease activity were also analyzed. In addition, resistin expression in lung specimens from patients with DM-ILD was examined immunohistochemistry and immunofluorescence.
Resistin mRNA levels in PBMCs were significantly higher in DM-ILD than that in DM patients without ILD and HCs ( = 0.043, 0.014, respectively). Among these DM-ILD patients, the resistin levels were significantly elevated in those with rapidly progressive ILD than in those with chronic ILD ( = 0.012). The resistin mRNA levels in DM-ILD positively correlated with serum alanine aminotransferase (r = 0.476, = 0.003), aspartate aminotransferase (r = 0.488, = 0.002), lactate dehydrogenase (r = 0.397, = 0.014), C-reactive protein (r = 0.423, = 0.008), ferritin (r = 0.468, = 0.003), carcinoembryonic antigen (r = 0.416, = 0.011), carbohydrate antigen 125 (r = 0.332, = 0.047), interleukin-18 (r = 0.600, < 0.001), and lung visual analog scale values (r = 0.326, = 0.048), but negatively correlated with the diffusing capacity of carbon monoxide (DLco)% (r = -0.447, = 0.041). Immunohistochemical analysis of resistin showed its elevated expression in the macrophages, alveolar epithelial cells, and weak fibrotic lesions from patients with DM-ILD. Immunofluorescence staining confirmed CD68+ macrophages co-express resistin.
Resistin levels were increased in patients with DM-ILD and associated with disease activity and ILD severity. Therefore, resistin may participate in the pathogenesis of DM-ILD and may act as a useful biomarker.
在本研究中,我们旨在评估伴间质性肺病的皮肌炎患者(DM-ILD)外周血单个核细胞(PBMC)中抵抗素mRNA水平及其与疾病活动度的相关性。
我们通过定量逆转录实时聚合酶链反应分析,检测了37例DM-ILD患者、8例无ILD的DM患者和19名健康对照(HC)受试者PBMC中的抵抗素mRNA水平。还分析了抵抗素表达水平与主要临床表现、实验室检查及疾病活动度之间的关联。此外,采用免疫组织化学和免疫荧光法检测了DM-ILD患者肺组织标本中抵抗素的表达。
DM-ILD患者PBMC中的抵抗素mRNA水平显著高于无ILD的DM患者和HC(分别为P = 0.043,P = 0.014)。在这些DM-ILD患者中,快速进展性ILD患者的抵抗素水平显著高于慢性ILD患者(P = 0.012)。DM-ILD患者的抵抗素mRNA水平与血清丙氨酸氨基转移酶(r = 0.476,P = 0.003)、天冬氨酸氨基转移酶(r = 0.488,P = 0.002)、乳酸脱氢酶(r = 0.397,P = 0.014)、C反应蛋白(r = 0.423,P = 0.008)、铁蛋白(r = 0.468,P = 0.003)、癌胚抗原(r = 0.416,P = 0.011)、糖类抗原125(r = 0.332,P = 0.047)、白细胞介素-18(r = 0.600,P < 0.001)及肺部视觉模拟量表值(r = 0.326,P = 0.048)呈正相关,但与一氧化碳弥散量(DLco)%呈负相关(r = -0.447,P = 0.041)。抵抗素的免疫组织化学分析显示,其在DM-ILD患者的巨噬细胞、肺泡上皮细胞及轻度纤维化病变中表达升高。免疫荧光染色证实CD68 +巨噬细胞共表达抵抗素。
DM-ILD患者的抵抗素水平升高,且与疾病活动度及ILD严重程度相关。因此,抵抗素可能参与DM-ILD的发病机制,并且可能作为一种有用的生物标志物。