CPCCRN PRECISE Supplement

项目摘要/摘要 儿科脓毒症诱导多器官功能障碍综合征(PRECISE)研究中的个性化免疫调节 由NICHD的儿科重症监护协作性研究网络(CPCCRN)进行的使用REAL- 根据受试者的免疫表型将受试者分配到治疗或观察队列的时间免疫表型 状态。这项24个地点、1000名受试者的精确研究目前使用的是全血体外脂多糖诱导的肿瘤坏死因子α 生产能力(肿瘤坏死因子α反应)试验诊断严重的先天性免疫抑制，称为 “免疫麻痹”。诊断免疫麻痹的另一种方法是测量 循环单核细胞表面抗原提呈分子人类白细胞抗原-DR的表达 使用流式细胞术。本申请提出增加mhla-DR表达测量， 现在对于多中心的使用比最初的研究设计时更可行，到 精密免疫表型分型面板。尽管mhla-DR表达不会被用来驱动队列 它的加入将允许评估mhla-DR表达作为一种潜在的诊断工具， 可能会推动未来的治疗。这一点很重要，因为目前还没有FDA批准的实验室 诊断免疫麻痹的测试，如果准确的研究是阳性的，目前没有办法 迅速推广其结果。将MHLA-DR表达添加到数据集提供了唯一和时间- 了解是否存在等于肿瘤坏死因子α反应的mhla-DR表达阈值的机会有限 精确研究中使用的截断值；以及了解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，这将极大地加速免疫麻痹的进程。 向临床实验室提供诊断服务，以造福危重儿童。

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.