NEUTROPHIL PHENOTYPING IN PERIODIC AND CHRONIC ARTHRITIS

周期性和慢性关节炎中的中性粒细胞表型

• 批准号: 7381138
• 负责人: Michael B Centola
• 金额: $ 20.05万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381138
• 关键词: NEUTROPHIL; PHENOTYPING; PERIODIC; CHRONIC; ARTHRITIS

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。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，需要有敏感和特异的方法来评估疾病的活动性。选择性抑制病理反应中涉及的促炎细胞因子和白细胞的生物制剂是目前抑制许多这些疾病中的疾病活动的最有效手段之一。然而，这些药物并不是万能的。影响既有疾病特异性，也因患者而异。不幸的是，评估患者体内这些可溶性介质水平和细胞介质活性以支持这些化合物的使用和直接监测其功效的临床试验不可用。在我们的初步研究中，一系列炎症性疾病的分子谱分析揭示了疾病活动的关键调节因子和生物标志物，其表达变化与临床反应相关。这些结果支持了这样的假设，即分子筛选可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。我们开发了标准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。在本项目的下一阶段，我们将通过进行充分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在多大程度上可以提高医生更快速诊断和优化类风湿关节炎患者治疗的能力。与此同时，我们将继续开发必要的技术，用于临床样本的生物标志物筛选，并将这些结果转化为在我们和类似装备的CLIA认证设施中进行的实际临床试验。