NEUTROPHIL PHENOTYPING IN PERIODIC AND CHRONIC ARTHRITIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 为了确保自身免疫性和自身炎症性疾病的准确诊断和治疗，有必要有灵敏和特异的手段来评估疾病的活动性。选择性抑制参与病理反应的促炎细胞因子和白细胞的生物制剂目前是许多此类疾病中抑制疾病活动性的最有效手段之一。然而，这些药物并不是灵丹妙药。影响既因疾病而异，也因患者而异。不幸的是，临床试验无法评估患者体内的这些可溶性介质水平和细胞介质活性，从而支持这些化合物的使用并直接监测其疗效。在我们的初步研究中，对一系列炎症性疾病的分子图谱揭示了疾病活动的关键调节因子和生物标志物，它们的表达变化与临床反应相关。这些结果支持这样一种假设，即分子筛查可以用于开发诊断和疾病活动监测测试，这将有助于优化和个性化治疗，从而为患者带来更好的结果。我们制定了标准的操作程序和实验室实践，并获得了原型疾病活动监测测试的临床实验室改进修正案(CLIA)认证。在这个项目的下一阶段，我们将通过进行足够有力的结果研究来进一步解决这一假设，以确定基因表达和细胞因子监测可以在多大程度上提高医生更快诊断和优化类风湿性关节炎患者治疗的能力。同时，我们将继续开发对临床样本进行生物标记物筛选所需的技术，并将这些结果转化为实际的临床测试，以便在我们的类似设备的CLIA认证设施中进行。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To assure accurate diagnosis and treatment of autoimmune and autoinflammatory diseases it is necessary to have sensitive and specific means to evaluate disease activity. Biologic agents that selectively inhibit proinflammatory cytokines and leukocytes involved in pathologic responses are currently among the most efficacious means of suppressing disease activity in many of these disorders. However, these agents are not a panacea. Effects are both disease-specific and vary among patients. Unfortunately, clinical tests to assess these soluble mediator levels and cellular mediator activities en masse in patients to support the use and monitor the efficacy of these compounds directly are not available. In our preliminary studies, molecular profiling of a spectrum of inflammatory diseases revealed key regulators and biomarkers of disease activity whose expression changes correlated with clinical response. These results support the hypothesis that molecular screening can be used to develop diagnostic and disease activity monitoring tests that will aid in the optimization and personalization of treatments, resulting in better outcomes for patients. We developed standard operating procedures and lab practices, and obtained Clinical Laboratory Improvement Amendments (CLIA) certification for a prototype disease activity-monitoring test. In the next phase of this project we will address this hypothesis further by performing adequately powered outcome studies to determine the extent to which gene expression and cytokine monitoring can enhance the ability of physicians to more rapidly diagnose and optimize treatment of rheumatoid arthritis patients. In parallel we will continue to develop the technologies necessary for biomarker screening of clinical samples and translation of these results into practicable clinical tests to be performed in our, and similarly equipped, CLIA-certified facilities.