CPCCRN PRECISE Supplement

CPCCRN 精确补充

• 批准号: 10884070
• 负责人: Jonathan Michael Dean
• 金额: $ 17.4万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-13 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10884070
• 关键词: Acceleration; Administrative Supplement; Adopted; Adoption; Adult; Antigen Presentation; Biological Assay; Blood specimen; Caring; Cells; Cessation of life; Child; Child Care; Childhood; Clinical; Collection; Communities; Critical Care; Critically ill children; Data; Data Coordinating Center; Data Set; Diagnosis; Diagnostic; Dose; Equation; Evaluation; Event; FDA approved; Failure; Flow Cytometry; Functional disorder; Funding; Future; Granulocyte-Macrophage Colony-Stimulating Factor; HLA Antigens; HLA-DR Antigens; Immune; Immune Tolerance; Immunologic Stimulation; Immunological Diagnosis; Immunophenotyping; Immunosuppression; Laboratories; Lipopolysaccharides; Logistics; Manufacturer; Measurement; Measures; Methods; Morbidity - disease rate; Movement; Multiple Organ Failure; National Institute of Child Health and Human Development; Organ; Outcome; Patients; Pharmaceutical Preparations; Phenotype; Placebos; Production; Protocols documentation; Research; Research Design; Route; Sampling; Sepsis; Site; Study Subject; Surface; TNF gene; Testing; Therapeutic; Time; Whole Blood; adverse outcome; clinical diagnostics; cohort; cost; cytokine; design; diagnostic tool; efficacy testing; immunological status; immunoregulation; immunostimulatory therapy; improved outcome; innate immune function; monocyte; mortality; outcome prediction; pediatric sepsis; primary outcome; response; routine care; septic; temporal measurement; treatment arm; treatment response

Project Summary/Abstract The Personalized Immunomodulation in Pediatric Sepsis-induced MODS (PRECISE) study that is currently being conducted by the NICHD’s Collaborative Pediatric Critical Care Research Network (CPCCRN) uses real- time immune phenotyping to assign subjects to treatment or observational cohorts based on their immune status. The 24-site, 1000-subject PRECISE study currently uses the whole blood ex vivo LPS-induced TNFα production capacity (TNFα response) assay to diagnose severe innate immune suppression, termed “immunoparalysis”. An alternative approach to diagnosing immunoparalysis is the measurement of the expression of the antigen-presenting molecule HLA-DR on the surface of circulating monocytes (mHLA-DR) using flow cytometry. The current application proposes the addition of mHLA-DR expression measurement, which is now much more feasible for multi-center use than at the time of the original study design, to the PRECISE immunophenotyping panel. Though mHLA-DR expression will not be used to drive cohort assignment, its addition will allow for the evaluation of mHLA-DR expression as a potential diagnostic tool that could drive treatment in the future. This is important because there are currently no FDA-approved laboratory tests for the diagnosis of immunoparalysis, and if the PRECISE study is positive, there is currently no way to rapidly generalize its results. The addition of mHLA-DR expression to the dataset provides a unique and time- limited opportunity to understand if thresholds of mHLA-DR expression exist that equate to the TNFα response cutoff used in the PRECISE study; and to understand if mHLA-DR expression can serve as a predictor of a favorable response to GM-CSF. If positive, this could greatly accelerate the movement of immunoparalysis diagnostics to the clinical laboratory, to the benefit of critically ill children.

项目总结/摘要 目前正在进行的儿科脓毒症诱导的MODS的个性化免疫调节（PRECISE）研究 正在进行的NICHD的合作儿科重症监护研究网络（CPCCRN）使用真实的- 根据受试者的免疫表型将其分配至治疗或观察队列的时间 status. 24家临床试验机构、1000例受试者的PRECISE研究目前使用全血离体LPS诱导的TNFα 生产能力（TNFα反应）测定诊断严重先天性免疫抑制，称为 “免疫麻痹”。诊断免疫麻痹的另一种方法是测量免疫球蛋白。 抗原呈递分子HLA-DR在循环单核细胞表面的表达（mHLA-DR） 使用流式细胞术。本申请提出增加mHLA-DR表达测量， 现在多中心使用比原始研究设计时更可行， PRECISE免疫表型检测试剂盒。尽管mHLA-DR表达将不用于驱动队列 分配，它的增加将允许评估mHLA-DR表达作为一个潜在的诊断工具， 可以推动未来的治疗。这一点很重要，因为目前没有FDA批准的实验室 免疫麻痹的诊断测试，如果PRECISE研究是阳性的，目前没有办法 快速推广其结果。将mHLA-DR表达添加到数据集中提供了独特的时间- 了解是否存在等同于TNFα反应的mHLA-DR表达阈值的机会有限 PRECISE研究中使用的截止值;并了解mHLA-DR表达是否可以作为预测 对GM-CSF的反应良好。如果呈阳性，这将大大加速免疫麻痹的发展 诊断到临床实验室，以造福危重患儿。