Predictors of Disease Progression in Human Lupus Syndromes

我们已经启动了一项针对不完全狼疮综合征（ILE）患者的研究， SLE的早期阶段（1）。ILE亚组研究相对不足，可能的结果也不清楚。 知道的已发表的研究很少，而且在这是否是一种稳定的、相对良性的 表型或是否可能进行性过程。现有数据表明，ILE亚组是 异质性，并且这些个体的子集将进展为SLE。我们假设， 患者包括处于进展性疾病的早期阶段的亚组，所述进展性疾病最终发展为SLE。我们 建议确定ILE人群的临床和免疫学稳定性（或不稳定性），并确定 这些生物标志物可预测进行性疾病进程。我们认为， ILE的疾病进展将导致可靠的SLE早期诊断方法。我们的长期目标是 制定战略，以便及早可靠地查明受益于 治疗干预，以防止器官损伤。 我们提出三个目标： 目的1：确定与表型最相关的细胞变化和自身抗体谱 不完全性狼疮（ILE）患者的进展。 目的2：探索类肽芯片识别ILE进展者的潜力。最新推出的类肽 阵列技术将被应用于检测抗体库中的变化，其规模大于 蛋白质阵列，并且其对已知抗原没有偏见。 目的3：确定最能预测表型的SLAM单倍型和转录组学变化 不完全性狼疮患者的进展。 该项目的长期目标是制定方法，以确定个人与前， 临床SLE。这将使研究设计可行，以测试具有潜在治疗效果的治疗方法。 预防和治疗。

We have initiated a research focus on patients with incomplete lupus syndromes, or ILE,to develop insights into early stages of SLE (1). The ILE subset is relatively understudied and the likely outcomes are not known. Published studies are small and conflicting in terms of whether this is a stable, relatively benign phenotype or whether a progressive course is likely. The available data suggest that the ILE subset is heterogeneous, and that a subset of these individuals will progress to SLE. We hypothesize that such patients include a subset who are in the early stages of a progressive illness that culminates in SLE. We propose to determine the clinical and immunologic stability (or instability) of the ILE population and to identify biomarkers that are predictive of a progressive disease course. We believe that identification of markers of disease progression in ILE will lead to approaches to reliable, early diagnosis of SLE. Our long term goal is the development of strategies for early and reliable identification of individuals who would benefit from therapeutic interventions to prevent organ damage. We propose three aims: Aim 1: To determine the cellular changes and autoantibody profiles that are best associated with phenotypic progression in incomplete lupus (ILE)patients. Aim 2: To explore the potential of peptoid arrays to identify ILE progressors. The newly available peptoid array technology will be applied to detect shifts in the antibody repertoire on a scale that is larger than the protein array and which is not biased for known antigens. Aim 3: To determine the SLAM haplotypes and transcriptomic changes that best predict phenotypic progression in incomplete lupus patients. The long term goals of this project are to develop approaches to the identification of individuals with pre- clinical SLE. This would make feasible the design of studies to test therapeutic approaches with potential for prevention and cure.