Development of a Point of Care Diagnostic Screening test for Kawasaki disease

ABSTRACT Kawasaki DiseaseKDis a febrile childhood vasculitis with potentially catastrophic clinical outcomesUntreatedone in five children develop coronary artery aneurysms causing significant morbidity and mortalityTypical KD presents as a febrile illness andgtdays in children andltyears oldThere are no diagnostic tests for KDit is diagnosed clinically based on a fever andgtdays with at leastofphysical findingsPediatricians who have not seen and treated KD tend to be insecure about making a KD diagnosisHoweversending home a child with KD can be disastrousHelping pediatricians make a diagnosis of KD is therefore a vital unmet medical needWe recently published a study of KD subjects and showed thatunlike other febrile conditionsKD is characterized by an elevated serum level of sTNFRIIapproximatelyfold higher than normalReference laboratory tests for sTNFRII are no longer available and had long turnaround times when they wereWe propose to develop a point of care test based on sTNFRII that can be used in pediatriciansoffices and emergency departments to rapidly and reliably exclude the diagnosis of KD in febrile childrenWe will develop lateral flow chromatography devices capable of detecting sTNFRII in human serum samples in a semiquantitative mannerThese devices will be based on existing polyclonal and monoclonal antibodies against sTNFRIIWe will also derive new rat monoclonal antibodies to increase the number of reagents at our disposal and to ensure optimal sensitivity and specificityThe performance of the lateral flow assay devices will be measured on human serum spiked with known concentrations of recombinant sTNFRIIIf the devices allow the user to distinguish a normal from an elevated concentration of sTNFRIIwe will analyze serum samples from our published study to confirm that the point of care test gives results identical to reference laboratory testsIf Phase I is successfulthe lateral flow devices will be used in Phase II experiments organized around a multicenter clinical trial NARRATIVE Kawasaki disease is a disease of children that can have devastating consequences and even be fatal within days if not correctly diagnosedWe have recently shown that patients with Kawasaki disease have an elevated serum level of sTNFRIIWe propose to develop a rapid test measuring sTNFRII that could be run by emergency departments and pediatricians in their officeThis would help in the rapid and cost effective diagnosis of Kawasaki disease