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骨桥蛋白在脑脊液中作为神经精神性系统性红斑狼疮诊断标志物的效用。

Utility of osteopontin in cerebrospinal fluid as a diagnostic marker for neuropsychiatric systemic lupus erythematosus.

作者信息

Kitagori K, Yoshifuji H, Oku T, Ayaki T, Kuzuya A, Nakajima T, Akizuki S, Nakashima R, Murakami K, Ohmura K, Hirayama Y, Takahashi R, Mimori T

机构信息

1 Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

2 Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

出版信息

Lupus. 2019 Mar;28(3):414-422. doi: 10.1177/0961203319828818. Epub 2019 Feb 11.

Abstract

The whole protein of osteopontin (OPN full) and its cleaved form (OPN N-half) are involved in the immune response and the migration of immune cells to an inflammatory lesion. We have reported that serum OPN full and urine OPN N-half are elevated in lupus nephritis (LN). Neuropsychiatric systemic lupus erythematosus (NPSLE) is a refractory complication of SLE. To investigate whether OPN full and OPN N-half could serve as diagnostic markers for NPSLE, and to elucidate their role in NPSLE pathogenesis, the concentrations of OPN full and OPN N-half in cerebrospinal fluid (CSF) were measured in NPSLE and non-NPSLE patients. We found that the concentration of OPN full in the CSF was significantly higher in NPSLE than in non-NPSLE, and it decreased after treatment. When the cutoff value of OPN full in CSF was set to 963.4 ng/ml, the sensitivity and specificity for the diagnosis of NPSLE were 70% and 100%, respectively. The correlation analysis of OPN full, OPN N-half and various cytokines/chemokines suggested that the cytokines/chemokines could be divided into two clusters: cluster A, which contains OPN full and cluster B, which contains interleukin-6. OPN full in CSF could be a novel diagnostic marker for NPSLE.

摘要

骨桥蛋白的完整蛋白(骨桥蛋白全长,OPN full)及其裂解形式(骨桥蛋白N端片段,OPN N-half)参与免疫反应以及免疫细胞向炎症病灶的迁移。我们曾报道,狼疮性肾炎(LN)患者血清中的骨桥蛋白全长和尿液中的骨桥蛋白N端片段水平升高。神经精神性系统性红斑狼疮(NPSLE)是系统性红斑狼疮(SLE)的一种难治性并发症。为了研究骨桥蛋白全长和骨桥蛋白N端片段是否可作为NPSLE的诊断标志物,并阐明它们在NPSLE发病机制中的作用,我们检测了NPSLE患者和非NPSLE患者脑脊液(CSF)中骨桥蛋白全长和骨桥蛋白N端片段的浓度。我们发现,NPSLE患者脑脊液中骨桥蛋白全长的浓度显著高于非NPSLE患者,且治疗后降低。当脑脊液中骨桥蛋白全长的截断值设定为963.4 ng/ml时,诊断NPSLE的敏感性和特异性分别为70%和100%。骨桥蛋白全长、骨桥蛋白N端片段与各种细胞因子/趋化因子的相关性分析表明,细胞因子/趋化因子可分为两个簇:簇A包含骨桥蛋白全长,簇B包含白细胞介素-6。脑脊液中的骨桥蛋白全长可能是NPSLE的一种新型诊断标志物。

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