Department of Renal and Rheumatology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
Clin Rheumatol. 2018 Oct;37(10):2675-2684. doi: 10.1007/s10067-018-4138-7. Epub 2018 May 17.
Increased IFN-γ levels have been associated with systemic lupus erythematosus (SLE). However, the relationships among IFN-γ, type I interferons (IFNs) and clinical features have not been extensively studied. Peripheral blood samples from 44 SLE patients and 36 healthy donors (HDs) were collected. Quantitative real-time PCR was used to assess the mRNA expression of IFNG, type II IFN-inducible genes (IRF1, GBP1, CXCL9, CXCL10, and SERPING1, which are used for the type II IFN score), type I IFN-inducible genes (IRF7, MX1, ISG15, and ISG20, which are used for the type I IFN score), TBX21, and EOMES in peripheral blood mononuclear cells. Flow cytometry was used to measure the IFN-γ levels in lymphocytes. The mRNA levels of type II IFN-inducible genes, IFNG, TBX21, and EOMES were significantly higher in SLE patients than those in HDs. Similarly, the percentages of IFN-γ-producing cells in lymphocytes and their subsets in SLE patients were significantly increased. Linear regression indicated that IFNG expression levels and type II IFN scores were positively correlated with anti-double-stranded DNA autoantibody levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. Compared with patients with low type I IFN scores, patients with high type I IFN scores showed increased type II IFN scores and SLEDAI scores. Type II IFN scores were positively associated with type I IFN scores. The IFN-γ signaling pathway is activated in SLE patients and may be considered an index of disease activity. IFN-γ, together with type I IFNs, promotes the pathogenesis of SLE.
IFN-γ 水平升高与系统性红斑狼疮（SLE）有关。然而，IFN-γ、I 型干扰素（IFN）和临床特征之间的关系尚未得到广泛研究。收集了 44 例 SLE 患者和 36 例健康对照者（HD）的外周血样本。采用实时定量 PCR 检测外周血单个核细胞中 IFNG、II 型 IFN 诱导基因（IRF1、GBP1、CXCL9、CXCL10 和 SERPING1，用于 II 型 IFN 评分）、I 型 IFN 诱导基因（IRF7、MX1、ISG15 和 ISG20，用于 I 型 IFN 评分）、TBX21 和 EOMES 的 mRNA 表达。采用流式细胞术检测淋巴细胞中 IFN-γ水平。与 HD 相比，SLE 患者外周血中 II 型 IFN 诱导基因、IFNG、TBX21 和 EOMES 的 mRNA 水平明显升高。同样，SLE 患者淋巴细胞及其亚群中 IFN-γ 产生细胞的比例也明显增加。线性回归分析表明，IFNG 表达水平和 II 型 IFN 评分与抗双链 DNA 自身抗体水平和系统性红斑狼疮疾病活动指数（SLEDAI）评分呈正相关。与低 I 型 IFN 评分患者相比，高 I 型 IFN 评分患者的 II 型 IFN 评分和 SLEDAI 评分升高。II 型 IFN 评分与 I 型 IFN 评分呈正相关。IFN-γ 信号通路在 SLE 患者中被激活，可作为疾病活动的指标。IFN-γ 与 I 型 IFNs 一起促进 SLE 的发病机制。
