Joint Academic Rheumatology Program, First Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Front Immunol. 2019 Mar 15;10:487. doi: 10.3389/fimmu.2019.00487. eCollection 2019.
Increased expression of type I interferon (IFN)-regulated genes has been described in blood and tissue cells from patients with systemic lupus erythematosus (SLE) and other rheumatic disorders. Only isolated studies have examined the type I IFN gene expression in antiphosholipid syndrome (APS), while efforts to evaluate associations with APS-related factors are scarce. Our aim was to investigate the type I IFN signature in patients with primary APS (PAPS), SLE/APS, and SLE in comparison with healthy controls, and to evaluate associations with disease-related characteristics. We measured the type I IFN score, derived from relative expressions of three IFN-inducible genes (MX-1, IFIT-1, and IFI-44) in peripheral blood mononuclear cells from 55 patients with PAPS, 34 with SLE/APS, 48 with SLE, and 28 controls. In patients with PAPS, we performed multivariate regression to examine associations of type I IFN score with their clinical, laboratory and treatment characteristics. Type I IFN score was increased in all patient groups vs. controls ( = 0.028, = 0.027, = 0.028 for PAPS, SLE/APS, and SLE, respectively). IFI-44 had the most pronounced expression. In patients with PAPS, multivariate linear regression revealed positive associations of type I IFN score with female gender (b-coefficient = 0.49; 95% CI 0.04, 0.94; = 0.034) and IgG or IgM anti-β2GPI antibodies (b-coefficient = 0.53; 95% CI 0.10, 0.96; = 0.017), and negative associations with age (b-coefficient = -0.02/year; 95% CI -0.04, -0.01; = 0.027) and hydroxychloroquine use (b-coefficient = -0.51; 95% CI-0.96, -0.06; = 0.027). Type I IFN score is increased in PAPS and correlated positively with anti-β2GPI antibodies and negatively with hydroxychloroquine use.
已有研究描述了红斑狼疮(SLE)和其他风湿性疾病患者的血液和组织细胞中 I 型干扰素(IFN)调节基因的表达增加。仅有一些孤立的研究探讨了抗磷脂综合征(APS)中的 I 型 IFN 基因表达,而评估其与 APS 相关因素之间关联的研究则很少。我们的目的是比较原发性 APS(PAPS)、SLE/APS 和 SLE 患者与健康对照者之间的 I 型 IFN 特征,并评估与疾病相关特征的关联。我们测量了外周血单个核细胞中三种 IFN 诱导基因(MX-1、IFIT-1 和 IFI-44)的相对表达,得到 I 型 IFN 评分,用于评估 55 例 PAPS 患者、34 例 SLE/APS 患者、48 例 SLE 患者和 28 例对照者的 I 型 IFN 评分。在 PAPS 患者中,我们进行了多变量回归分析,以检查 I 型 IFN 评分与他们的临床、实验室和治疗特征之间的关联。与对照组相比,所有患者组的 I 型 IFN 评分均升高(PAPS、SLE/APS 和 SLE 组的差异分别为 = 0.028、= 0.027 和 = 0.028)。IFI-44 的表达最明显。在 PAPS 患者中,多元线性回归显示 I 型 IFN 评分与女性性别(β系数=0.49;95%置信区间 0.04-0.94;=0.034)和 IgG 或 IgM 抗-β2GPI 抗体(β系数=0.53;95%置信区间 0.10-0.96;=0.017)呈正相关,与年龄(β系数=-0.02/年;95%置信区间-0.04 至-0.01;=0.027)和羟氯喹使用(β系数=-0.51;95%置信区间-0.96 至-0.06;=0.027)呈负相关。PAPS 患者的 I 型 IFN 评分升高,与抗-β2GPI 抗体呈正相关,与羟氯喹的使用呈负相关。