Biomarkers for the discrimination of acute kawasaki disease from infections in childhood
Author(s)
Zandstra, Judith
van de Geer, Annemarie
Tanck, Michael WT
Dimitriades, Diana van Stijn-Bringas
Aarts, Cathelijn EM
Type
Journal Article
Abstract
Background: 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.
Methods and Results: 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 (n = 48) from patients with infection (n = 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 (n = 26) from those with infections (n = 150), with an AUC of 0.78. The second validation cohort of acute KD patients (n = 25) and febrile controls (n = 50) showed an AUC of 0.72, which improved to 0.84 when HNE was included.
Conclusion: 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.
Methods and Results: 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 (n = 48) from patients with infection (n = 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 (n = 26) from those with infections (n = 150), with an AUC of 0.78. The second validation cohort of acute KD patients (n = 25) and febrile controls (n = 50) showed an AUC of 0.72, which improved to 0.84 when HNE was included.
Conclusion: 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.
Date Issued
2020-07-22
Date Acceptance
2020-05-28
Citation
Frontiers in Pediatrics, 2020, 8
ISSN
2296-2360
Publisher
Frontiers Media
Journal / Book Title
Frontiers in Pediatrics
Volume
8
Copyright Statement
© 2020 Zandstra, van de Geer, Tanck, van Stijn-Bringas Dimitriades, Aarts, Dietz, van Bruggen, Schweintzger, Zenz, Emonts, Zavadska, Pokorn, Usuf, Moll, Schlapbach, Carrol, Paulus, Tsolia, Fink, Yeung, Shimizu, Tremoulet, Galassini, Wright, Martinón-Torres, Herberg, Burns, Levin, Kuijpers, EUCLIDS Consortium, PERFORM Consortium and UK Kawasaki Disease Genetics Study Network. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000560073900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Pediatrics
kawasaki disease
infectious disease
vasculitis
coronary aneurysm
biomarker
bacterial infection
viral infection
C-REACTIVE PROTEIN
RISK-FACTORS
EXPRESSION
ACTIVATION
ASSOCIATION
SENSITIVITY
DIAGNOSIS
CHILDREN
MARKER
Publication Status
Published
Article Number
ARTN 355
Date Publish Online
2020-07-22