AUTHOR=Zandstra Judith , van de Geer Annemarie , Tanck Michael W. T. , van Stijn-Bringas Dimitriades Diana , Aarts Cathelijn E. M. , Dietz Sanne M. , van Bruggen Robin , Schweintzger Nina A. , Zenz Werner , Emonts Marieke , Zavadska Dace , Pokorn Marko , Usuf Effua , Moll Henriette A. , Schlapbach Luregn J. , Carrol Enitan D. , Paulus Stephane , Tsolia Maria , Fink Colin , Yeung Shunmay , Shimizu Chisato , Tremoulet Adriana , Galassini Rachel , Wright Victoria J. , Martinón-Torres Federico , Herberg Jethro , Burns Jane , Levin Michael , Kuijpers Taco W. ,  EUCLIDS Consortium, PERFORM Consortium and UK Kawasaki Disease Genetics Study Network 

TITLE=Biomarkers for the Discrimination of Acute Kawasaki Disease From Infections in Childhood

JOURNAL=Frontiers in Pediatrics

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2020.00355

DOI=10.3389/fped.2020.00355

ISSN=2296-2360

ABSTRACT=<p><bold>Background:</bold> Kawasaki disease (KD) is a vasculitis of early childhood mimicking several infectious diseases. Differentiation between KD and infectious diseases is essential as KD's most important complication—the development of coronary artery aneurysms (CAA)—can be largely avoided by timely treatment with intravenous immunoglobulins (IVIG). Currently, KD diagnosis is only based on clinical criteria. The aim of this study was to evaluate whether routine C-reactive protein (CRP) and additional inflammatory parameters myeloid-related protein 8/14 (MRP8/14 or S100A8/9) and human neutrophil-derived elastase (HNE) could distinguish KD from infectious diseases.</p><p><bold>Methods and Results:</bold> The cross-sectional study included KD patients and children with proven infections as well as febrile controls. Patients were recruited between July 2006 and December 2018 in Europe and USA. MRP8/14, CRP, and HNE were assessed for their discriminatory ability by multiple logistic regression analysis with backward selection and receiver operator characteristic (ROC) curves. In the discovery cohort, the combination of MRP8/14+CRP discriminated KD patients (<italic>n</italic> = 48) from patients with infection (<italic>n</italic> = 105), with area under the ROC curve (AUC) of 0.88. The HNE values did not improve discrimination. The first validation cohort confirmed the predictive value of MRP8/14+CRP to discriminate acute KD patients (<italic>n</italic> = 26) from those with infections (<italic>n</italic> = 150), with an AUC of 0.78. The second validation cohort of acute KD patients (<italic>n</italic> = 25) and febrile controls (<italic>n</italic> = 50) showed an AUC of 0.72, which improved to 0.84 when HNE was included.</p><p><bold>Conclusion:</bold> When used in combination, the plasma markers MRP8/14, CRP, and HNE may assist in the discrimination of KD from both proven and suspected infection.</p>