Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Inserm UMRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France
Centre Hospitalier Universitaire de Dijon, Hôpital François-Mitterrand, service de médecine interne et maladies systémiques (médecine interne 2), Dijon, France.
Ann Rheum Dis. 2019 Dec;78(12):1669-1676. doi: 10.1136/annrheumdis-2019-215571. Epub 2019 Sep 30.
Maintenance of remission has become central in the management of systemic lupus erythematosus (SLE). The importance of interferon-alpha (IFN-α) in the pathogenesis of SLE notwithstanding, its expression in remission has been poorly studied as yet. To study its expression in remission and its prognostic value in the prediction of a disease relapse, serum IFN-α levels were determined using an ultrasensitive single-molecule array digital immunoassay which enables the measurement of cytokines at physiological concentrations.
A total of 254 SLE patients in remission, according to the Definition of Remission in SLE classification, were included in the study. Serum IFN-α concentrations were determined at baseline and patients were followed up for 1 year. Lupus flares were defined according to the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index Flare Index, whereas the Kaplan-Meier analysis and Cox regression analysis were used to estimate the time to relapse and to identify baseline factors associated with time to relapse, respectively.
Of all patients in remission, 26% displayed abnormally high IFN-α serum levels that were associated with the presence of antibodies specific for ribonucleoprotein (RNP), double stranded (ds)DNA and Ro/SSA60, as well as young age. Importantly, elevated-baseline IFN-α serum levels and remission duration were associated in an independent fashion, with shorter time to relapse, while low serum levels of complement component 3 and anti-dsDNA Abs were not.
Direct serum IFN-α assessment with highly sensitive digital immunoassay permits clinicians to identify a subgroup of SLE patients, clinically in remission, but at higher risk of relapse.
维持缓解已成为系统性红斑狼疮(SLE)治疗的核心。尽管干扰素-α(IFN-α)在 SLE 发病机制中具有重要作用,但迄今为止,对其在缓解期的表达及其在预测疾病复发方面的预后价值研究甚少。为了研究其在缓解期的表达及其在预测疾病复发方面的预后价值,我们使用超灵敏单分子阵列数字免疫分析测定了血清 IFN-α 水平,该方法可在生理浓度下测量细胞因子。
本研究共纳入 254 例根据 SLE 缓解定义处于缓解期的 SLE 患者。在基线时测定血清 IFN-α 浓度,并对患者进行了 1 年的随访。狼疮发作根据雌激素在红斑狼疮中的安全性:系统性红斑狼疮疾病活动指数 flares 索引的全国评估版本进行定义,Kaplan-Meier 分析和 Cox 回归分析分别用于估计复发时间和识别与复发时间相关的基线因素。
在所有缓解期患者中,26%的患者血清 IFN-α 水平异常升高,这与抗核糖核蛋白(RNP)、双链(ds)DNA 和 Ro/SSA60 特异性抗体的存在以及年龄较小有关。重要的是,基线时升高的 IFN-α 血清水平和缓解持续时间与复发时间独立相关,而补体成分 3 和抗 dsDNA Abs 血清水平较低则与复发时间无关。
使用超灵敏数字免疫分析直接测定血清 IFN-α,可使临床医生识别出一组临床缓解但复发风险较高的 SLE 患者。