个性化免疫检测揭示分子网络，有助狼疮患者的分类
Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients
Source：Cell
Volume165, Issue 3, 21 April 2016, Pages 551–565
要点
Highlights
•长达4年时间针对158例狼疮患者的临床及转录分析
•Clinical and transcriptionalprofiling of 158 lupus patients up to a period of 4 years
• 中性粒细胞相关标志与活动性肾炎的进展有关
•Neutrophil-related signatures associate with progression to active nephritis
• 根据分子相关疾病活动将病人分层为七种主要类型
•Molecular correlates ofdisease activity stratify patients into seven major groups
• 分子分层可能提高SLE(系统性红斑狼疮)的临床试验结果
•Molecular stratification mayimprove the outcome of clinical trials in SLE
摘要
Summary
系统性红斑狼疮（SLE）是一种自身免疫性疾病，特点是抗核酸能力的丧失和高度多样化的临床表现。为评估其分子异质性，我们利用158名患儿的血液进行了转录组学表达的纵向研究。采用混合模型来考虑重复测量，统计，治疗，疾病活动度（DA），和肾炎分类，我们证实了一个普遍存在的IFN标记物，并鉴别出与DA最为相关的浆母细胞标记。我们检测出活动性肾炎进展过程中逐步增多的中性粒细胞转录本，以及不同亚型肾炎对治疗应答的独特标记物。重要的是，个性化免疫检测有助个性化地监测疾病活动度，并根据患者的基因型细分为7个亚组，并被患者基因型支持。我们的研究揭示了SLE的分子异质性，并解释了临床试验失败的原因。对于基因学和临床上较为复杂的自身免疫性疾病，这种方法可以改进相关临床试验设计，以及个性化治疗方法的实施。
Systemic lupus erythematosus (SLE)is an autoimmune disease characterized by loss of tolerance to nucleic acidsand highly diverse clinical manifestations. To assess its molecularheterogeneity, we longitudinally profiled the blood transcriptome of 158pediatric patients. Using mixed models accounting for repeated measurements,demographics, treatment, disease activity (DA), and nephritis class, weconfirmed a prevalent IFN signature and identified a plasmablast signature asthe most robust biomarker of DA. We detected gradual enrichment of neutrophiltranscripts during progression to active nephritis and distinct signatures inresponse to treatment in different nephritis subclasses. Importantly,personalized immunomonitoring uncovered individual correlates of diseaseactivity that enabled patient stratification into seven groups, supported bypatient genotypes. Our study uncovers the molecular heterogeneity of SLE andprovides an explanation for the failure of clinical trials. This approach mayimprove trial design and implementation of tailored therapies in geneticallyand clinically complex autoimmune diseases.
大昂仔 译 / Jason 校对
2016/5/6
