Activation of the interferon-α pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease
Activation of the interferon-α pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease
复制标题
DOI：
10.1002/art.21031
复制
发表时间：
2005-05-01
影响因子：
--
通讯作者：
Crow, MK
中科院分区：
文献类型：
--
作者：
Kirou, KA;Lee, C;Crow, MK
目标。基因表达研究表明，许多系统性红斑狼疮（SLE）患者外周血单个核细胞（PBMCs）中干扰素（IFN）诱导基因（IFIGs）的表达增加，其中I型IFN的作用最为明显。本研究检验了一种假设，即疾病严重程度和活动性的增加，以及不同的自身抗体特异性，是SLE患者I型IFN通路激活的特征。从77名SLE患者、22名疾病对照者和28名健康供者中新分离的pbmc对IFN α优先诱导的3种ifg进行实时聚合酶链反应，并使用这些数据获得所有个体的IFN α评分。与疾病对照组或健康供者相比，SLE患者中IFIGs的表达明显更高。通过双变量和多变量分析，比较IFN α评分高和低的SLE患者的疾病临床表现、疾病严重程度、疾病活动性、血清学特征和潜在混杂因素。与IFN α评分较低的SLE患者相比，IFN α评分较高的SLE患者有更高的肾脏疾病患病率，更多的美国风湿病学会SLE标准，以及更高的系统性狼疮国际合作诊所损害指数（SDI）评分。通过较低的C3水平、血红蛋白水平、绝对淋巴细胞计数和白蛋白水平以及较高的抗双链DNA （dsDNA）滴度、红细胞沉降率和SLE疾病活动指数2000评分来衡量，得分高的患者疾病活动性增加。存在针对Ro， U1 RNP， Sm和dsDNA的抗体，而不是磷脂的抗体，与高IFN α评分显著相关。Logistic回归分析证实，肾脏疾病、较高的SDI评分、低补体水平和抗rna结合蛋白（RBP）自身抗体的存在与较高的IFN α评分相关。IFN α途径的激活定义了SLE患者的一个亚组，其病情特征是疾病严重程度增加，包括肾脏疾病，疾病活动性增加，反映在补体激活和对RBP的自身反应性。
Objective. Gene-expression studies have demonstrated increased expression of interferon (IFN)inducible genes (IFIGs) in peripheral blood mononuclear cells (PBMCs) of many patients with systemic lupus erythematosus (SLE), with a predominant effect of type I IFN. This study examined the hypothesis that increased disease severity and activity, as well as distinct autoantibody specificities, characterize SLE patients with activation of the type I IFN pathway.Methods. Freshly isolated PBMCs from 77 SLE patients, 22 disease controls, and 28 healthy donors were subjected to real-time polymerase chain reaction for 3 IFIGs that are preferentially induced by IFN alpha, and the data were used to derive IFN alpha scores for all individuals. Expression of IFIGs was significantly higher in SLE patients compared with disease controls or healthy donors. SLE patients with high and low IFN alpha scores were compared for clinical manifestations of disease, disease severity, disease activity, serologic features, and potential confounders, by bivariate and multivariate analyses.Results. SLE patients with a high IFN alpha score had a significantly higher prevalence of renal disease, a greater number of American College of Rheumatology criteria for SLE, and a higher Systemic Lupus International Collaborating Clinics damage index (SDI) score than did SLE patients with low IFN alpha scores. Patients with high scores showed increased disease activity, as measured by lower C3 levels, hemoglobin levels, absolute lymphocyte counts, and albumin levels, and a higher anti-double-stranded DNA (dsDNA) titer, erythrocyte sedimentation rate, and SLE Disease Activity Index 2000 score. The presence of antibodies specific for Ro, U1 RNP, Sm, and dsDNA, but not phospholipids, was significantly associated with a high IFN alpha score. Logistic regression analysis confirmed that renal disease, higher SDI scores, low complement levels, and presence of anti-RNA binding protein (RBP) autoantibodies were associated with a high IFN alpha score.Conclusion. Activation of the IFN alpha pathway defines a subgroup of SLE patients whose condition is characterized by increased disease severity, including renal disease, increased disease activity, reflected in complement activation, and autoreactivity to RBP.