Patient-oriented research in skin autoimmune disease

描述(由申请人提供)：本提案的科学重点是红斑狼疮(LE)的患者导向研究(POR)。我们的实验室研究了LE的光敏遗传学(由VA Merit审查支持)，以及LE开发新疗法所需的基本POR(目前的提议)。我们最近的研究正在开发和验证测量皮肤LE活动和严重程度所需的结果指标。目的一、扩展评价者间和评价者内的验证研究我们目前发表的针对少量患者的研究，评估皮肤科医生认为，皮肤红斑狼疮疾病活动和严重程度指数(CLASI)对皮肤LE活性和损害的测量具有很好的评价者间和评价者内的可变性。重要的是扩大目前已经进行的研究，以纳入更多的患者，包括那些皮肤发生急性LE变化的患者，向更多的皮肤科医生验证Clasi，并将研究扩大到包括风湿病医生。拟议的研究将使进展到AIM II，这涉及到使用CLASI来评估大量皮肤红斑狼疮患者的转诊人群，以及生活质量研究和POR翻译研究。目的II.需要新干预措施的皮肤红斑狼疮的临床严重程度的患病率，皮肤红斑狼疮的生活质量(QOL)测量，以及CLASI与QOL测量的相关性。目前有许多新的治疗方法应该在皮肤红斑狼疮患者中进行测试。我们最近完成的一项前瞻性研究显示，Clasi在药物干预后具有良好的反应性。Clasi的改善与患者和医生对皮肤健康的全球衡量标准的改善相关。随着该仪器最近可用于量化特定皮肤的LE疾病活动和损害，以及特定于皮肤的生活质量(QOL)指数(Skindex 29)，并且经过AIM I中建议的进一步验证研究，现在可以评估正在使用现有药物的患者的疾病严重程度。因此，在这项应用中，建议使用皮肤病活动量化工具和生活质量测量来横断面评估皮肤LE的亚组。其目的将是检查皮肤红斑狼疮的不同亚型的严重程度，他们的生活质量，以及生活质量测量与CLASI的相关性。特别是，有必要评估有多少严重皮肤红斑狼疮患者目前正在经历重大疾病，尽管使用了现有的药物，以便评估新疗法的必要性和设计新药物的试验。这将促进未来的遗传学、重点关注的微阵列和聚合酶链式反应研究，以及与皮肤红斑狼疮亚型相关的机制研究。这些研究将允许进一步仔细验证Clasi，并有助于规划未来的试验。

DESCRIPTION (provided by applicant): The scientific focus of this proposal is patient-oriented research (POR) in lupus erythematosus (LE). Our laboratory studies the genetics of photosensitivity in LE (supported by a VA Merit Review), as well as fundamental POR needed for development of new therapies in LE (the current proposal). Our recent studies are developing and validating outcome measures needed for measuring cutaneous LE activity and severity. Aim I. Expansion of inter-rater and intra-rater validation studies Our current published studies with a small number of patients and evaluating dermatologists suggest excellent inter-rater and intra-rater variability with the cutaneous lupus erythematosus disease activity and severity index (CLASI) measure of cutaneous LE activity and damage. It is important to expand the current studies that have been done to include more patients, including those with acute LE changes in the skin, to validate the CLASI with both more dermatologists, and to extend the studies to include rheumatologists. The proposed studies will allow progression to Aim II, which involves use of the CLASI to evaluate large referral populations of cutaneous LE patients, in addition to quality of life studies and POR translational studies. Aim II. Prevalence of clinical severity of cutaneous lupus erythematosus requiring novel interventions, quality of life (QOL) measurement of cutaneous LE and the correlation of the CLASI with QOL measurement. There are currently a number of new therapies that should be tested in patients with cutaneous LE. A prospective study we recently completed showed excellent responsiveness of the CLASI after drug intervention. Improvement in the CLASI correlated with improvement in both patient and physician global measures of skin health. With the recent availability of this instrument to quantify skin-specific LE disease activity and damage, as well as a quality of life (QOL) index specific to skin (Skindex 29), and after further validation studies proposed in Aim I, it is now possible to evaluate the severity of disease in patients who are using currently available drugs. Thus, it is proposed in this application to use tools for quantifying skin disease activity and QOL measurements to cross-sectionally evaluate subsets of cutaneous LE. The purpose will be to examine the severity of various subsets of cutaneous LE, their QOL, and the correlation of the QOL measures with the CLASI. In particular, it is necessary to evaluate how many patients with severe cutaneous LE are currently experiencing significant disease despite use of available agents, in order to assess the need for new therapies and to design trials of new agents. This will facilitate future genetic, focused microarray and PCR studies, as well as mechanistic studies related to subsets of cutaneous lupus erythematosus. These studies will allow further careful validation of the CLASI, as well as aid in planning of future trials.