权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The Vasculitis of Kawasaki Disease

川崎病血管炎

基本信息

批准号：
9060257
负责人：
ANNE H ROWLEY
金额：
$ 17.2万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9060257
关键词：
Acute Affect Age Aneurysm Arteritis Autopsy Biological Assay Biological Markers Blood Vessels C-reactive protein CXCL13 gene CXCL14 gene Cell Proliferation Child Childhood Chronic Cicatrix Complication Coronary Coronary Aneurysm Coronary Arteriosclerosis Coronary artery Data Development Erythrocyte Sedimentation Rate Exanthema Extracellular Protein Fever Future Gender Genes Goals Grant Health Immune Immune Response Genes Immune Sera Immune response Inflammation Inflammatory Response Injection of therapeutic agent Interleukin-18 Lead Limb structure Link Lymphatic Diseases Lymphocyte Medial Molecular Monitor Morbidity - disease rate Mucocutaneous Lymph Node Syndrome Multicenter Studies Necrotizing Arteritides Onset of illness Operative Surgical Procedures Pathogenesis Pathologic Pathology Pathway interactions Patient Care Patients Phase Pilot Projects Plasma Cells Process Proteins RNA Research Support Reverse Transcriptase Polymerase Chain Reaction Seminal Serum Serum Markers Smooth Muscle Myocytes Stenosis Symptoms Testing Time Tissues Up-Regulation Vasculitis Wound Healing adverse outcome base candidate marker cohort collaborative trial eosinophil high risk immune activation improved inflammatory marker insight mortality potential biomarker prevent transcriptome vascular inflammation

项目摘要

DESCRIPTION (provided by applicant): Kawasaki Disease (KD) is a potentially fatal vasculitis of young childhood. Although the initial presenting symptoms of fever, exanthem, enanthem, conjunctival injection, extremity changes, and adenopathy are self- limiting, our recent seminal pathologic study of autopsy or surgical arterial tissues from 41 KD patients demonstrated subacute/chronic vasculitis persisting for months to years after the onset. Chronic KD vasculitis was not recognized in early pathologic studies of KD, and children with persistent coronary artery aneurysms do not receive additional immunomodulatory therapies after the acute febrile phase of illness. We hypothesize that prolonged immune activation contributes to persistent coronary arteritis in KD patients, and that markers of immune activation can be detected in the sera of KD children with persistent coronary artery aneurysms. In preliminary studies, we demonstrated upregulation of more than 20 immune response genes by real-time RT- PCR analyses of coronary artery tissues from 7 KD patients with persistent aneurysms (>6 months to years after the onset) and 7 childhood controls. In separate preliminary studies, we performed transcriptome analysis of 8 KD and 7 childhood control coronary arteries (2.5 weeks to 5 months after the onset) and identified 1057 dysregulated genes (q-value <0.05 and >1.5 fold change). These dysregulated genes included ~50 immune response genes that are upregulated in KD vascular tissues and encode extracellular proteins that are candidate serum biomarkers of chronic KD vasculitis. In a subsequent pilot study, we tested sera from 6 KD children with persistent (3-8 years after onset) coronary artery aneurysms and from 6 childhood controls for levels of 15 of these 50 proteins and identified 5 candidate serum markers of persistent KD vasculitis. In this exploratory proposal, we will: 1) Identify molecular pathways dysregulated in chronic KD vasculitis tissues, and 2) Identify serum immune biomarkers of chronic KD vasculitis. The results of these studies will provide important insights into the molecular immunopathogenesis of chronic KD vasculitis, and enable development of a panel of serum biomarkers of chronic KD vasculitis that can be tested in larger multicenter patient cohorts. Such non-invasive markers could enable identification and monitoring of KD patients with chronic vasculitis for participation in future multicenter collaborative trials of immunomodulatory therapies, to reduce morbidity and mortality from this serious childhood illness.

描述（由申请方提供）：川崎病（KD）是一种可能致命的幼儿血管炎。虽然最初的表现症状发热，出疹，出疹，结膜充血，肢体变化和腺病是自限性的，我们最近对41名KD患者的尸检或手术动脉组织进行的开创性病理学研究表明，亚急性/慢性血管炎在发病后持续数月至数年。慢性KD血管炎在KD的早期病理学研究中未被识别，患有持续性冠状动脉瘤的儿童在疾病的急性发热期后未接受额外的免疫调节治疗。我们假设，长期的免疫激活有助于KD患者持续性冠状动脉炎，免疫激活的标志物可以在KD儿童持续性冠状动脉瘤的血清中检测到。在初步研究中，我们通过实时RT-PCR分析来自7名患有持续性动脉瘤（发病后>6个月至数年）的KD患者和7名儿童对照的冠状动脉组织，证实了20多种免疫应答基因的上调。在单独的初步研究中，我们对8支KD和7支儿童对照冠状动脉（发病后2.5周至5个月）进行了转录组分析，并确定了1057个失调基因（q值<0.05 and >1.5倍变化）。这些失调的基因包括约50种免疫应答基因，这些基因在KD血管组织中上调，并编码细胞外蛋白，这些蛋白是慢性KD血管炎的候选血清生物标志物。在随后的初步研究中，我们检测了6名患有持续性（发病后3-8年）冠状动脉瘤的KD儿童和6名儿童对照的血清中这50种蛋白质中的15种蛋白质的水平，并确定了5种持续性KD血管炎的候选血清标志物。在这个探索性的建议中，我们将：1）确定慢性KD血管炎组织中失调的分子通路，2）确定慢性KD血管炎的血清免疫生物标志物。这些研究的结果将为慢性KD血管炎的分子免疫发病机制提供重要见解，并能够开发一组慢性KD血管炎的血清生物标志物，这些生物标志物可以在更大的多中心患者队列中进行测试。这些非侵入性标志物可以识别和监测慢性血管炎KD患者，以便参与未来的免疫调节治疗多中心合作试验，以降低这种严重儿童疾病的发病率和死亡率。