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