Monitoring Disease Activity in Systemic Lupus Erythematosus With Single-Molecule Array Digital Enzyme-Linked Immunosorbent Assay Quantification of Serum Interferon-
Monitoring Disease Activity in Systemic Lupus Erythematosus With Single-Molecule Array Digital Enzyme-Linked Immunosorbent Assay Quantification of Serum Interferon-
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DOI：
10.1002/art.40792
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发表时间：
2019-05-01
影响因子：
13.3
通讯作者：
Amoura, Zahir
中科院分区：
文献类型：
--
作者：
Mathian, Alexis;Mouries-Martin, Suzanne;Amoura, Zahir
目的在常规临床实践中，没有一种简单或标准化的方法可以定量检测干扰素。单分子阵列(SIMOA)数字酶联免疫吸附分析(ELISA)技术使干扰素能够在全摩尔浓度(每毫升[Fg/ml])下直接定量。为评价干扰素数字化ELISA法在系统性红斑狼疮(SLE)活动性监测中的诊断价值。方法采用数字化酶联免疫吸附试验(DELISA法)和功能生物活性测定法(BIO法)对连续150例SLE患者血清中的干扰素浓度进行检测。根据系统性红斑狼疮疾病活动指数(SLEDAI)综合评分中雌激素的安全性，将患者分为非活动期SLE组(SLEDAI评分0分)、无活动期SLE组、轻、中、重度活动期SLE组。结果根据健康献血者的血清标本，血清干扰素水平异常阈值为136fg/ml。其次，使用受试者操作特征曲线，对疾病活动和器官受累具有广泛异质性的SLE患者系列，与活动期疾病相关的阈值干扰素水平被确定为266 fg/ml，数字酶联免疫吸附试验评估的血清干扰素水平是一个比FARR法更好的疾病活动性生物标志物，因为其特异性、阳性结果的似然比和阳性预测值更好地区分活动期和非活动期疾病。结论用高灵敏度的血清干扰素直接检测血清干扰素，可更好地监测SLE的临床活动性，选择最佳的抗干扰素治疗方案。
ObjectiveNo simple or standardized assay is available to quantify interferon- (IFN) in routine clinical practice. Single-molecule array (Simoa) digital enzyme-linked immunosorbent assay (ELISA) technology enables direct IFN quantification at attomolar (femtogram per milliliter [fg/ml]) concentrations. This study was undertaken to assess IFN digital ELISA diagnostic performances to monitor systemic lupus erythematosus (SLE) activity.MethodsIFN concentrations in serum samples from 150 consecutive SLE patients in a cross-sectional study were determined with digital ELISA and a functional biologic activity assay (bioassay). According to their Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) flare composite scores, patients were divided into groups with inactive SLE (SLEDAI score of 0), and into groups with no flare or mild/moderate flare or severe flare.ResultsBased on serum samples from healthy blood donors, the abnormal serum IFN level threshold value was 136 fg/ml. Next, using receiver operating characteristic curves for an SLE patient series that was widely heterogeneous in terms of disease activity and organ involvement, the threshold IFN value associated with active disease was determined to be 266 fg/ml. The digital ELISA-assessed serum IFN level was a better biomarker of disease activity than the Farr assay because its specificity, likelihood ratio for positive results, and positive predictive value better discerned active SLE or flare from inactive disease. The digital ELISA was more sensitive than the bioassay for detecting low-abnormal serum IFN concentrations and identifying patients with low disease activity.ConclusionDirect serum IFN determination with a highly sensitive assay might improve monitoring of clinical SLE activity and selection of the best candidates for anti-IFN treatment.