Frontiers in Pediatrics (Jul 2020)
Biomarkers for the Discrimination of Acute Kawasaki Disease From Infections in Childhood
- Judith Zandstra,
- Annemarie van de Geer,
- Michael W. T. Tanck,
- Diana van Stijn-Bringas Dimitriades,
- Cathelijn E. M. Aarts,
- Sanne M. Dietz,
- Robin van Bruggen,
- Nina A. Schweintzger,
- Werner Zenz,
- Marieke Emonts,
- Dace Zavadska,
- Marko Pokorn,
- Effua Usuf,
- Henriette A. Moll,
- Luregn J. Schlapbach,
- Enitan D. Carrol,
- Stephane Paulus,
- Maria Tsolia,
- Colin Fink,
- Shunmay Yeung,
- Shunmay Yeung,
- Chisato Shimizu,
- Adriana Tremoulet,
- Rachel Galassini,
- Victoria J. Wright,
- Federico Martinón-Torres,
- Jethro Herberg,
- Jane Burns,
- Michael Levin,
- Taco W. Kuijpers,
- Taco W. Kuijpers,
- EUCLIDS Consortium, PERFORM Consortium and UK Kawasaki Disease Genetics Study Network
Affiliations
- Judith Zandstra
- Sanquin Research and Landsteiner Laboratory, Department of Immunopathology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
- Annemarie van de Geer
- Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
- Michael W. T. Tanck
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
- Diana van Stijn-Bringas Dimitriades
- Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
- Cathelijn E. M. Aarts
- Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
- Sanne M. Dietz
- Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
- Robin van Bruggen
- Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
- Nina A. Schweintzger
- Department of General Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
- Werner Zenz
- Department of General Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
- Marieke Emonts
- Pediatric Infectious Diseases and Immunology Department, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
- Dace Zavadska
- Department of Pediatrics, Riga Stradins University, Riga, Latvia
- Marko Pokorn
- Department of Infectious Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Effua Usuf
- Medical Research Council Unit the Gambia (MRCG) at LSHTM, Serrekunda, Gambia
- Henriette A. Moll
- 0Department of General Pediatrics, Erasmus MC—Sophia Children's Hospital, Rotterdam, Netherlands
- Luregn J. Schlapbach
- 1Pediatric Intensive Care Unit, Lady Cilento Children's Hospital, Pediatric Critical Care Research Group, Brisbane, QLD, Australia
- Enitan D. Carrol
- 2Department of Clinical Infection, Microbiology and Immunology, University of Liverpool Institute of Infection and Global Health, Liverpool, United Kingdom
- Stephane Paulus
- 2Department of Clinical Infection, Microbiology and Immunology, University of Liverpool Institute of Infection and Global Health, Liverpool, United Kingdom
- Maria Tsolia
- 3Second Department of Pediatrics, P. & A. Kyriakou Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece
- Colin Fink
- 4Micropathology Ltd., University of Warwick, Warwick, United Kingdom
- Shunmay Yeung
- 5Department of Clinical Research, Faculty of Infectious and Tropical Disease, London School of Hygiene and Tropical Medicine, London, United Kingdom
- Shunmay Yeung
- 6Section of Paediatric Infectious Diseases, Department of Infectious Disease, Imperial College London, London, United Kingdom
- Chisato Shimizu
- 7Kawasaki Disease Research Center, Rady's Children's Hospital—San Diego, University of California, San Diego, San Diego, CA, United States
- Adriana Tremoulet
- 7Kawasaki Disease Research Center, Rady's Children's Hospital—San Diego, University of California, San Diego, San Diego, CA, United States
- Rachel Galassini
- 6Section of Paediatric Infectious Diseases, Department of Infectious Disease, Imperial College London, London, United Kingdom
- Victoria J. Wright
- 6Section of Paediatric Infectious Diseases, Department of Infectious Disease, Imperial College London, London, United Kingdom
- Federico Martinón-Torres
- 8Translational Pediatrics and Infectious Diseases, Hospital Clínico Universitario de Santiago, University of Santiago, Santiago de Compostela, Spain
- Jethro Herberg
- 6Section of Paediatric Infectious Diseases, Department of Infectious Disease, Imperial College London, London, United Kingdom
- Jane Burns
- 7Kawasaki Disease Research Center, Rady's Children's Hospital—San Diego, University of California, San Diego, San Diego, CA, United States
- Michael Levin
- 6Section of Paediatric Infectious Diseases, Department of Infectious Disease, Imperial College London, London, United Kingdom
- Taco W. Kuijpers
- Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
- Taco W. Kuijpers
- Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
- EUCLIDS Consortium, PERFORM Consortium and UK Kawasaki Disease Genetics Study Network
- DOI
- https://doi.org/10.3389/fped.2020.00355
- Journal volume & issue
-
Vol. 8
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.
Keywords
