Proteomic Investigations in Kawasaki Disease

川崎病的蛋白质组学研究

基本信息

批准号：
7337324
负责人：
HARVEY J COHEN
金额：
$ 23.7万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-01-01 至 2009-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7337324
关键词：
Acute Affect Affinity Aneurysm Antibodies Binding Binding Proteins Biological Assay Biological Markers Cardiac Characteristics Child Clinical Coronary artery Development Diagnosis Diagnostic tests Dilatation - action Disease Early Diagnosis Etiology Fever Functional disorder Gel Grant Heart Diseases Hour Human IgY Immunoglobulin Therapy Immunoglobulins Individual Infant Inflammatory Intravenous Immunoglobulins Investigation Lasers Mass Spectrum Analysis Measures Methods Microspheres Modality Molecular Weight Monitor Mucocutaneous Lymph Node Syndrome Orphan Pathological Dilatation Patients Pattern Peptides Plasma Process Protein Binding Proteins Proteomics Rare Diseases Research Research Personnel Risk Sampling Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Surface Symptoms Testing Time Trypsin Two-Dimensional Gel Electrophoresis Urine Vasculitis base insight novel outcome forecast prevent programs protein aminoacid sequence response two-dimensional

项目摘要

DESCRIPTION (provided by applicant): Kawasaki Disease (KD) is an acute inflammatory vasculitis that affects infants and children. If not diagnosed and treated promptly with intravenous immunoglobulin (IVIG), KD can result in coronary artery dilatation or aneurysms. The diagnosis of KD is made on clinical grounds and there is no specific diagnostic test. Not only is there risk of sequellae in children with KD who are misdiagnosed and not treated, there are also risks associated with unnecessary IVIG treatment in children who do not have KD. Therefore, there is a need for a sensitive and specific diagnostic test. The characteristic systemic signs associated with KD suggest that specific patterns of plasma or urine proteins (biomarkers) may be associated with the disease. Identification of these proteins may give better insight to the pathophysiology of KD, and even give clues to its etiology. Protein patterns may also be predictive of responsiveness to IVIG therapy, may help explain the mechanism of IVIG therapy or predict the development of coronary artery dilatation or aneurysms. The hypotheses being tested in this proposal are: 1) There are proteins in plasma or urine characteristic of KD (biomarkers) that can distinguish children with KD from those with other febrile illnesses, and that some of these proteins are at least partially bound to IG (Specific Aim 1). 2) IVIG affects the amount of these free peptide or protein biomarkers in the plasma or urine of patients with KD (Specific Aim 2). We will begin to test the hypotheses that those individuals with KD who have or develop coronary artery dilatation or aneurysms have a distinct protein pattern in their plasma or urine and that protein patterns at the time of diagnosis can identify those children whose disease will respond to IVIG (Specific Aim 3). Although beyond the scope of this proposal, we further hypothesize that some of these proteins/peptides are involved in the pathophysiology and symptoms associated with KD, and that the mechanism by which IG relieves these symptoms is by binding these proteins/peptides. The successful completion of the aims of this proposal will then from the basis for answering this important mechanistic question. This proposal is in response to an NHLBI request for novel investigations in "orphan" heart diseases. The potentially clinically devastating cardiac consequences of KD and the importance of early diagnosis in preventing them encouraged us to develop and test new modalities to aid in diagnosis, and potentially prognosis of this relatively rare disease.

描述（由申请人提供）：川崎病（KD）是一种影响婴儿和儿童的急性炎症性血管炎。如果未通过静脉内免疫球蛋白（IVIG）及时诊断和治疗，KD会导致冠状动脉扩张或动脉瘤。 KD的诊断是基于临床理由进行的，没有特定的诊断测试。 KD患有误诊和未接受治疗的KD儿童不仅存在次序的风险，而且在没有KD的儿童的不必要的IVIG治疗中也存在风险。因此，需要进行敏感且特定的诊断测试。与KD相关的特征系统迹象表明，血浆或尿液蛋白（生物标志物）的特定模式可能与该疾病有关。这些蛋白质的鉴定可能可以更好地了解KD的病理生理学，甚至可以为其病因提供线索。蛋白质模式也可以预测对IVIG疗法的反应性，可能有助于解释IVIG治疗的机制或预测冠状动脉扩张或动脉瘤的发展。在该提案中进行了检验的假设是：1）血浆或尿液特征（生物标志物）中有蛋白质，可以将KD儿童与患有其他高潮疾病的儿童区分开来，并且其中一些蛋白质至少部分与Ig（特定AIM 1）结合。 2）IVIG会影响KD患者血浆或尿液中这些游离肽或蛋白质生物标志物的量（特定目标2）。我们将开始检验以下假设：那些患有或发展冠状动脉扩张或动脉瘤的人在血浆或尿液中具有独特的蛋白质模式，并且诊断时的蛋白质模式在其血浆或尿液中具有独特的蛋白质模式。尽管除了该提案的范围之外，我们进一步假设这些蛋白质/肽中的某些与KD相关的病理生理和症状涉及，并且Ig减轻这些症状的机制是通过结合这些蛋白质/肽来结合这些症状。然后，该提案的目标成功完成将从回答这个重要的机械性问题的基础。该建议是对NHLBI要求“孤儿”心脏病的新型调查的要求。 KD的潜在临床灾难性心脏后果以及早期诊断在防止它们方面的重要性，鼓励我们发展和测试新的方式，以帮助诊断，并可能对这种相对罕见的疾病进行预后。