Kawasaki Disease (KD) is a febrile childhood vasculitis with potentially catastrophic clinical outcomes. Untreated, one in five children develop coronary artery aneurysms causing significant morbidity and mortality. Typical KD presents as a febrile illness >4 days in children <5 years old. There are no diagnostic tests for KD; it is diagnosed clinically based on a fever >4 days with at least 4 of 5 physical findings. Pediatricians who have not seen and treated KD tend to be insecure about making a KD diagnosis. However, sending home a child with KD can be disastrous. Helping pediatricians make a diagnosis of KD is therefore a vital unmet medical need. We recently published a study of KD subjects and showed that, unlike other febrile conditions, KD is characterized by an elevated serum level of sTNFRII, approximately 2-20-fold higher than normal. Reference laboratory tests for sTNFRII are no longer available and had long turnaround times when they were. We propose to develop a point-of-care test based on sTNFRII that can be used in pediatricians? offices and emergency departments to rapidly and reliably exclude the diagnosis of KD in febrile children. We will develop lateral-flow chromatography devices capable of detecting sTNFRII in human serum samples in a semi- quantitative manner. These devices will be based on existing polyclonal and monoclonal antibodies against sTNFRII. We will also derive new rat monoclonal antibodies to increase the number of reagents at our disposal and to ensure optimal sensitivity and specificity. The performance of the lateral-flow assay devices will be measured on human serum spiked with known concentrations of recombinant sTNFRII. If the devices allow the user to distinguish a normal from an elevated concentration of sTNFRII, we will analyze serum samples from our published study to confirm that the point-of-care test gives results identical to reference laboratory tests. If Phase I is successful, the lateral-flow devices will be used in Phase II experiments organized around a multicenter clinical trial.
Kawasaki disease is a disease of children that can have devastating consequences and even be fatal within days if not correctly diagnosed. We have recently shown that patients with Kawasaki disease have an elevated serum level of sTNFRII. We propose to develop a rapid test measuring sTNFRII that could be run by emergency departments and pediatricians in their office. This would help in the rapid and cost-effective diagnosis of Kawasaki disease.
