AstraZeneca, Gaithersburg, MD, USA.
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sci Rep. 2019 Oct 8;9(1):14433. doi: 10.1038/s41598-019-50231-y.
Systemic lupus erythematosus (SLE) impacts multiple organ systems, although the causes of many individual SLE pathologies are poorly understood. This study was designed to elucidate organ-specific inflammation by identifying proteins that correlate with SLE organ involvement and to evaluate established biomarkers of disease activity across a diverse patient cohort. Plasma proteins and autoantibodies were measured across seven SLE manifestations. Comparative analyses between pathologies and correlation with the SLE Disease Activity Index (SLEDAI) were used to identify proteins associated with organ-specific and composite disease activity. Established biomarkers of composite disease activity, SLE-associated antibodies, type I interferon (IFN), and complement C3, correlated with composite SLEDAI, but did not significantly associate with many individual SLE pathologies. Two clusters of proteins were associated with renal disease in lupus nephritis samples. One cluster included markers of infiltrating leukocytes and the second cluster included markers of tissue remodelling. In patients with discoid lupus, a distinct signature consisting of elevated immunoglobulin A autoantibodies and interleukin-23 was observed. Our findings indicate that proteins from blood samples can be used to identify protein signatures that are distinct from established SLE biomarkers and SLEDAI and could be used to conveniently monitor multiple inflammatory pathways present in different organ systems.
系统性红斑狼疮（SLE）影响多个器官系统，尽管许多个体 SLE 病理学的原因尚不清楚。本研究旨在通过鉴定与 SLE 器官受累相关的蛋白质来阐明器官特异性炎症，并在多样化的患者队列中评估疾病活动的既定生物标志物。在七个 SLE 表现中测量了血浆蛋白和自身抗体。对病理之间的比较分析以及与 SLE 疾病活动指数（SLEDAI）的相关性用于鉴定与器官特异性和复合疾病活动相关的蛋白质。复合疾病活动的既定生物标志物、与 SLE 相关的抗体、I 型干扰素（IFN）和补体 C3 与复合 SLEDAI 相关，但与许多个体 SLE 病理相关性不大。两个与狼疮肾炎样本中肾脏疾病相关的蛋白质簇。一个簇包括浸润白细胞的标志物，第二个簇包括组织重塑的标志物。在盘状狼疮患者中，观察到由升高的免疫球蛋白 A 自身抗体和白细胞介素 23 组成的独特特征。我们的研究结果表明，来自血液样本的蛋白质可用于鉴定与既定的 SLE 生物标志物和 SLEDAI 不同的蛋白质特征，并且可用于方便地监测不同器官系统中存在的多种炎症途径。
