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，以发展洞察力 进入SLE的早期阶段(1)。ILE子集的研究相对较少，可能的结果也没有 为人所知。就这是否是一种稳定、相对良性的疾病而言，已发表的研究规模很小，而且相互矛盾 表型或是否可能有进展性病程。现有数据表明，ILE子集是 异质性，这些个体中的一部分将发展为SLE。我们假设这样的情况 患者包括处于进展性疾病的早期阶段，最终发展为SLE的患者。我们 建议确定ILE人群的临床和免疫稳定性(或不稳定性)，并确定 预测疾病进展过程的生物标记物。我们认为，标记物的识别 ILE的疾病进展将导致对SLE进行可靠的早期诊断。我们的长期目标是 制定战略，以便及早和可靠地确定将受益于 预防器官损伤的治疗性干预。 我们提出三个目标： 目标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：探索类肽阵列识别ILE进展因子的可能性。新上市的类肽 将应用阵列技术来检测抗体库中的变化，其规模将大于 蛋白质阵列，并且对已知抗原不存在偏见。 目的3：确定最能预测表型的SLAM单倍型和转录改变 不完全性狼疮患者的进展。 该项目的长期目标是开发识别患有前驱疾病的个人的方法。 临床型红斑狼疮。这将使研究设计成为可行的，以测试潜在的治疗方法 防病治病。

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.