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.

项目概要/摘要 目前正在进行的小儿败血症诱导的 MODS 个性化免疫调节 (PRECISE) 研究 由 NICHD 的儿科重症监护协作研究网络 (CPCCRN) 进行，使用真实的 时间免疫表型根据受试者的免疫情况将受试者分配到治疗组或观察组 24 个地点、1000 名受试者的 PRECISE 研究目前使用全血离体 LPS 诱导的 TNFα。 用于诊断严重先天免疫抑制的生产能力（TNFα反应）测定，称为 “免疫麻痹”是诊断免疫麻痹的另一种方法。 循环单核细胞表面抗原呈递分子 HLA-DR 的表达 (mHLA-DR) 使用流式细胞术，当前申请建议添加 mHLA-DR 表达测量， 现在比最初的研究设计时更适合多中心使用 精确的免疫表型分析面板虽然 mHLA-DR 表达不会用于驱动队列。 分配，其添加将允许评估 mHLA-DR 表达作为潜在的诊断工具 这很重要，因为目前还没有 FDA 批准的实验室。 诊断免疫麻痹的测试，如果 PRECISE 研究呈阳性，目前没有办法 快速概括其结果。将 mHLA-DR 表达添加到数据集中提供了独特且时间- 了解是否存在与 TNFα 反应相同的 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因子 对 GM-CSF 的良好反应如果呈阳性，这可能会大大加速免疫麻痹的进展。 临床实验室的诊断，以造福危重儿童。