A Comprehensive Model of Severity in Outcomes in Ankylosing Spondylitis

为了了解强直性脊柱炎患者的自然病史和预后，这项建议将研究多个 疾病结局模型中的成分。任何对这种疾病的真正理解都必须考虑到遗传 因素，疾病随时间的活跃度，新生物制剂的治疗，以及心理社会结构。 结果也是一个复杂的结构，考虑到患者报告的疼痛和功能因素 丢失，累积的放射损伤，以及病态事件，如髋关节置换等。 对这种疾病进行横断面评估的经验使我们以一种 一个模型，可以量化和检查每个因素对结果变量的相对重要性。在……里面 为了实现这一目标，我们提出了5个目标：1)我们将再招募和留住300名患者 截至任何病程，以补充已经招募的600名美国患者并保留这些 已经登记在正在进行的腰椎疾病队列中；2)我们将对675K个SNP进行分析，作为预测 1000名英国AS患者的疾病结局(以BASFI衡量)， 疾病活跃度(由BASDAI衡量)和发病年龄(病程)。这些675K 作为1000英国全基因组扫描的一部分，SNPs将被确定为疾病易感性的预测因子 项目1，目标2中执行的患者；3)我们将确认并扩展目标2中的观察结果 1500名美国患者作为SNPs患者，这些SNPs来自本方案和项目中AIM 2的输出 1，目标2。在这个目标中，我们将识别SNPs，这些SNPs可以预测患者的功能和放射学结果 来自北美的大量(900名患者)AS患者，已经或将会 在本项目的目标1中招聘和保留；4)我们将确定和审查 心理社会因素(应对、无助和情绪障碍)与疾病进展 已确定的队列(300名受试者)以及先前已确定的腰大肌队列的后续时间间隔 (400名受试者)；5)我们将检验遗传因素和所有其他非遗传因素的相对贡献 (在上面的目标2-4中提到)，使用开发的分析技术对这一队列的结果做出贡献 在本意见书的项目4中。预计疾病结局的非遗传成分和 进展(包括生物制剂的治疗)将能够被量化并检查其 对患者预后的相对重要性。

In order to understand the natural history and outcome of patients with AS, this proposal will study multiple ingredients in a model of disease outcome. Any true comprehension of this disease must consider genetic factors, disease activity over time, treatment with new biologic agents, and psychosocial constructs. Outcome is a complex construct as well, taking into account patient reported factors of pain and function loss, accumulated radiographic damage, and morbid events such as hip replacements, etc. Our previous experience in assessing this disease in a cross-sectional manner has led us to approach the question in a model that can quantify and examine each factor for its relative importance to the outcome variables. In order to accomplish this objective, we propose 5 Aims:1) we will recruit and retain 300 additional patients with AS of any disease duration to complement the 600 USA patients already recruited and to retain those already enrolled in the ongoing PSOAS cohort; 2) we will perform an analysis of 675K SNPs as predictors of disease outcome in 1000 UK patients with AS in terms of functional impairment (as measured by the BASFI), disease activity (as measured by the BASDAI) and age at disease onset (disease duration). These 675K SNPs will be identified as predictors for disease susceptibility as part of a genome wide scan in 1000 UK AS patients as performed in project 1, aim 2; 3) we will confirm and extend the observations from Aim 2 in a cohort of 1500 USA AS patients with SNPs derived from the output of Aim 2 in this proposal and from Project 1, Aim 2. In this aim we will identify SNPs that are predictive of functional and radiological outcomes in the large (900 patient) PSOAS cohort of AS patients from North America that either has already been or will be recruited and retained in Aim 1 of this project; 4) we will identify and examine the relationships between psychosocial factors (coping, helplessness, and mood disturbances) and progression of disease in our newly identified cohort (300 subjects) as well as in follow-up intervals of the previously identified PSOAS cohort (400 subjects); 5) we will examine the relative contributions of genetic and all of the other non-genetic factors (addressed in Aims 2-4 above) that contribute to outcome in this cohort using analytic techniques developed in Project 4 of this submission. It is anticipated that non-genetic components of disease outcome and progression (including treatments with biologic agents) will be able to be quantified and examined for their relative importance to patient outcome.