Proteomic Investigations in Kawasaki Disease
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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.
