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