Predictors of Disease Progression in Human Lupus Syndromes

人类狼疮综合征疾病进展的预测因子

• 批准号: 7941909
• 负责人: Nancy J Olsen
• 金额: $ 30.26万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7941909
• 关键词: Antibody Repertoire; Antigens; Autoantibodies; Benign; Biological Markers; Clinical; Conflict (Psychology); Data; Development; Disease Progression; Dissection; Early Diagnosis; Event; Genetic; Goals; Haplotypes; Human; Immunologics; Individual; Lead; Lupus; Mus; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Organ; Outcome; Pathogenesis; Patients; Phenotype; Population; Prevention; Progressive Disease; Protein Array; Publishing; Research; Research Design; Staging; Syndrome; Systemic Lupus Erythematosus; Technology; Testing; Therapeutic; Therapeutic Intervention; insight; man; novel; pre-clinical; prevent; transcriptomics

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.

我们已经开始研究不完整的狼疮综合症或ILE的患者以开发见解 进入SLE（1）的早期阶段。 ILE子集相对研究了，可能的结果不是 已知。公开的研究很小，就这是否是稳定的，相对良性的矛盾 表型或进步课程是否可能。可用的数据表明Ile子集是 异质性，这些人中的一部分将发展为SLE。我们假设这样 患者包括一个处于进展疾病早期阶段的子集，该子群在SLE中达到高潮。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 可以预测进行性疾病病程的生物标志物。我们相信识别的标记 ILE的疾病进展将导致对SLE的可靠，早期诊断的方法。我们的长期目标是 制定早期和可靠识别个人的策略，这些个人将从中受益 治疗干预措施以防止器官损伤。 我们提出了三个目标： 目的1：确定与表型最好相关的细胞变化和自身抗体曲线 不完全狼疮（ILE）患者的进展。 目标2：探索肽阵列的潜力以识别Ile Progressors。新的肽 阵列技术将用于检测抗体库中的变化，该量表大于 蛋白质阵列，并且对已知抗原没有偏见。 目标3：确定最能预测表型的大满贯单倍型和转录组变化 不完整狼疮患者的进展。 该项目的长期目标是开发识别患有预先的个体的方法 临床SLE。这将使可行的​​研究设计以测试具有潜力的治疗方法 防治。