Gene Expression as Predictors of Outcome in the GENISOS (Genetics vs Environm

系统性硬化症(SSC)是一种以纤维化、血管损伤和自身免疫为特征的慢性疾病 现象。病因尚不清楚，临床谱系也存在很大差异。我们的研究假设是 SSC的预后可以通过与临床、血清学和临床相关的基因表达谱来预测 遗传/种族因素以及社会人口特征。我们的具体目标如下：1) 对患者外周血基因表达谱和皮肤活检进行分类分析 早期局限性SSc、早期弥漫性SSc和匹配的健康对照组；2)比较血液中这些特征 弥漫性SSC稳定期患者的皮肤活检到早期弥漫性SSC的轮廓 纵向(个别患者内部)和横截面(独立患者之间) 群体)；3)扩大多种族(高加索人、西班牙人和非裔美国人)GENISOS早期疾病 纵向跟踪受试者疾病相关结局的SSC队列：4)描述队列的特征 根据人口学、种族-民族背景、临床疾病特征、自身抗体亚群、人类白细胞抗原 和其他基因测试，以及社会行为特征；5)使用AIMS 1的数据开发模型 通过4)识别患者亚类并预测预后；以及6)提供临床资料 支持该CORT的项目1的队列。设计和方法：有5年病史的自发性硬化症患者 将使用标准化表格进行登记，并按规定的间隔进行跟踪。连续的血液样本将会是 将对所有参与者进行皮肤活检，并对一些参与者进行皮肤活检。定制打印的50个寡核苷酸 将使用代表19,700个人类和208个拟南芥(阴性对照)基因的微阵列，并 将使用监督方法和类别比较来发现不同调控基因之间的差异 预定义的类别(例如，早期漫反射SSC与晚期漫反射SSC)。GEE分析将用于检查 结果之间的关系(例如，皮肤病病程、肺纤维化等)和独立的 变量(例如，人口统计、人类白细胞抗原、微阵列数据等)外行语言摘要：此项目将 研究最近发病的硬皮病患者，以确定区分这些患者的特征 会有轻微疾病的人会有更严重的病程。这些信息将帮助医生 患者决定适合他们的疾病水平的治疗计划。

Systemic sclerosis (SSc) is a chronic disease characterized by fibrosis, vascular damage, and autoimmune phenomena. The etiology is unknown and the clinical spectrum is highly variable. Our study HYPOTHESIS is that prognosis in SSc can be predicted by gene expression profiling correlated with clinical, serologic and genetic/ethnic factors as well as sociodemographic features. Our SPECIFIC AIMS are as follows: 1) To perform classification analysis of peripheral blood gene-expression-profiles and skin biopsies from patients with early limited SSc, early diffuse SSc and matched healthy controls; 2) To compare these profiles in blood and skin biopsies from patients in the stable chronic phase of diffuse SSc to profiles from early, diffuse SSc both longitudinally (within individual patients) and in cross-sectional fashion (between separate patient groups); 3) to expand the multi-ethnic (Caucasian, Hispanic, and African-American) GENISOS early-disease SSc cohort following subjects longitudinally for disease relevant outcomes: 4) to characterize the cohort according to demographics, racial-ethnic background, clinical disease features, autoantibody subsets, HLA and other genetic testing, and socio-behavioral features; 5) To develop a model using the data from aims 1 through 4 to identify subsets of patients and predict prognosis; and 6) to provide clinical material from this cohort to support Project 1 of this CORT. DESIGN and METHODS: SSc patients with <5 years of disease will be enrolled and followed at defined intervals using standardized forms. Serial blood samples will be obtained on all and skin biopsies will be done on some participants. Custom printed 50-oligonucleotide microarrays representing 19,700 human and 208 Arabidopsis (negative controls) genes will be used and supervised methods and class comparison will be used to discover differentially regulated genes between predefined classes (e.g., early diffuse SSc vs late diffuse SSc).GEE analysis will be used to examine the association between the outcomes (e.g..course of skin disease, pulmonary fibrosis, etc.) and independent variables (e.g., demographic, HLA, microarray data, etc.) LAY LANGUAGE SUMMARY: This project will study patients with the recent onset of scleroderma in order to identify features that distinguish those who will have mild disease from those who will have a more severe course. This information will help physicians and patients decide on a treatment plan that is appropriate for their level of disease.