Assessment in Morphea for the Establishment of Non-Cutaneous Disease (AMEND)

硬斑病是否存在非皮肤疾病的评估 (AMEND)

• 批准号: 7902056
• 负责人: Heidi T Jacobe
• 金额: $ 11.29万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7902056
• 关键词: Accounting; Address; Adult; Affect; Age; Area; Attention; Autoantibodies; Autoimmune Diseases; Autoimmune Process; Award; Case-Control Studies; Characteristics; Child; Childhood; Clinical; Clinical Investigator; Clinical Research; Clinical Sciences; Clinical and Translational Science Awards; Cohort Studies; Collaborations; Collection; Commit; Complement; Confusion; Control Groups; Cutaneous; Data; Databases; Defect; Deformity; Dermatology; Development; Disease; Disease Management; Disease Outcome; Disease Progression; Enrollment; Environment; Epidemiology; Evaluation; Face; Family history of; Frequencies; Funding; Future; Genetic; Genotype; Goals; Health Sciences; Immune; Immunogenetics; Institution; Joints; Lichen - organism; Limb structure; Measures; Medical center; Mentors; Monitor; Morphea; NCI Scholars Program; National Center for Research Resources; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Natural History; Outcome; Pain; Patients; Phase; Phenotype; Predictive Factor; Prevalence; Principal Investigator; Race; Recruitment Activity; Research; Research Personnel; Research Project Grants; Resources; Risk; Sampling; Science; Scleroderma; Sclerosis; Serological; Serum; Skin; Source; Staging; Subcutaneous Tissue; Syndrome; Systemic Scleroderma; Systemic disease; Testing; Texas; Time; Training; Training Activity; Training Programs; Translational Research; United States National Institutes of Health; Universities; Variant; Wages; biobank; career; case control; clinical phenotype; cohort; demographics; design; disease characteristic; disease natural history; epidemiology study; experience; follow-up; functional disability; genetic epidemiology; genetic profiling; human leukocyte antigen gene; insight; interest; outcome forecast; patient oriented research; prognostic; prospective; response; sex; skills; systemic autoimmune disease; trait

DESCRIPTION (provided by applicant): The purpose of this application is to support my advanced training in patient-oriented research with the goal of becoming an independently funded investigator studying the epidemiology, immune profiles, and genetics of morphea in adults and children. I will achieve this objective with the help of a rich and supportive environment at the University of Texas Southwestern Medical Center (my institution) which includes: an experienced mentoring committee representing national experts in my fields of interest; a robust training nfrastructure through the Department of Clinical Sciences' Clinical Scholars Program; and an NIH NCRR linded Clinical and Translational Science Award (CTSA) supporting clinical research. These local resources are complemented by the University of Texas Health Science Center in Houston, also the recipient of a TSA award directed by one of my principle mentors, Dr. Frank Arnett. The training program detailed herein as well as the proposed research, represent the inaugural collaborative efforts between two geographically adjacent CTSA centers; which is a mandate and priority for CTSA awards. The Department of Dermatology has committed its full support to my training as a clinical investigator through its sponsorship of my participation in the Clinical Scholars Program (which requires salary support and 75% protected time to pursue training and a research project), access to the departmental clinical research center as well and its outstanding research coordinator, and the active dermatology practice for subject recruitment. The mentored research project that I will conduct in conjunction with my formal training in clinical research nvolves the epidemiology, autoantibody profiles, and immunogenetics of morphea. Morphea is characterized by thickening and hardening of the skin affecting both adults and children and has serious sequelae in terms of joint, limb, and facial deformities producing pain and functional impairment. At this time, there is controversy regarding the exact implications of morphea in terms of its risk for the development of other diseases, either autoimmune or systemic; if there are characteristic autoantibodies or HLA types associated with the disease that may predict disease activity or outcome; and the natural history of the disease. This confusion impairs the appropriate treatment of morphea patients, who suffer serious consequences from either over or under treatment. Having gained initial research experience in this area, I aim to conduct a case control study examining the frequency of systemic and autoimmune disease, presence of autoantibodies, and HLA associations in morphea patients vs. healthy and scleroderma (putatively the systemic form of morphea) controls. Morphea subjects enrolled in the first phase of the study will be asked to continue in a prospective cohort study for ascertainment of the natural history of the disease and if the characteristics measured at baseline predict these outcomes. Design and implementation of this study along with the training activities listed above will develop skills in epidemiological research as well as the translational research skills necessary to investigate the mechanistic aspects of my discoveries including immunogenetics, autoantibody characterization, and genetic epidemiology, thus launching a successful career as an independent clinical investigator.

描述（由申请人提供）：本申请的目的是支持我在以患者为导向的研究方面的高级培训，目标是成为一名独立资助的研究人员，研究成人和儿童硬斑病的流行病学、免疫特征和遗传学。我将在德克萨斯大学西南医学中心（我的机构）丰富和支持性环境的帮助下实现这一目标，其中包括： 代表我感兴趣领域的国家专家的经验丰富的指导委员会；通过临床科学系的临床学者计划建立强大的培训基础设施；以及 NIH NCRR 授予的临床和转化科学奖 (CTSA)，支持临床研究。这些当地资源得到休斯敦德克萨斯大学健康科学中心的补充，该中心也是我的主要导师之一 Frank Arnett 博士指导下的 TSA 奖项的获得者。本文详细介绍的培训计划以及拟议的研究代表了两个地理位置相邻的 CTSA 中心之间的首次合作；这是 CTSA 奖项的任务和优先事项。皮肤科通过赞助我参加临床学者计划（该计划需要工资支持和 75% 的受保护时间来进行培训和研究项目）、进入系临床研究中心及其杰出的研究协调员、以及在受试者招募中积极进行皮肤病学实践，全力支持我作为临床研究者的培训。我将结合我的临床研究正式培训进行指导研究项目，涉及硬斑病的流行病学、自身抗体谱和免疫遗传学。硬斑病的特点是皮肤增厚和硬化，影响成人和儿童，并在关节、四肢和面部畸形方面产生严重的后遗症，产生疼痛和功能障碍。目前，关于硬斑病对其他疾病（无论是自身免疫性疾病还是全身性疾病）发展风险的确切影响存在争议。是否存在与疾病相关的特征性自身抗体或 HLA 类型，可以预测疾病活动或结果；以及疾病的自然史。这种混淆损害了硬斑病患者的适当治疗，他们因治疗过度或治疗不足而遭受严重后果。在获得了该领域的初步研究经验后，我的目标是进行一项病例对照研究，检查硬皮病患者与健康对照和硬皮病（推测为硬皮病的系统形式）对照中全身性和自身免疫性疾病的发生频率、自身抗体的存在以及 HLA 关联。参加第一阶段研究的硬斑病受试者将被要求继续进行前瞻性队列研究，以确定该疾病的自然史以及基线测量的特征是否可以预测这些结果。本研究的设计和实施以及上述培训活动将培养流行病学研究技能以及研究我的发现的机制方面所需的转化研究技能，包括免疫遗传学、自身抗体表征和遗传流行病学，从而开启作为独立临床研究者的成功职业生涯。