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

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 Zandstra et al. Discrimination Acute KD From Infections 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.

Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles

“…Although there are shared features between the response to KD and both bacterial and viral infections, the distinct pathways enriched in each disease group demonstrate the variation in the molecular host response; the distinctiveness of the responses is also supported by the ability of RNA and protein signatures to discriminate KD from bacterial and viral infections [ 18 , 19 , 35 ]. These differences between the response during KD and the responses to bacterial and viral infections suggest that KD may be triggered by a novel process not typical of either common bacterial or viral infections.…”

Biomarkers to predict infection and infection‐related complications during chemotherapy‐induced neutropenia in acute myeloid leukaemia: a pilot study

“…Neutropenic episodes were categorised by their course: samples taken in the absence of fever, during FN (mild FN), and during infection‐related complications requiring intensive care unit (ICU) treatment (complicated FN). We assessed the concentration of C‐reactive protein (CRP), 9,10 interleukin 8 (IL‐8), 9 human neutrophil elastase (HNE), 10 myeloid‐related protein‐8/14 (MRP8/14) 10 and nucleosomes 11 to predict infection, ICU admission and bone marrow recovery in patients with AML after high‐dose induction chemotherapy. During neutropenia, all patients received prophylaxis with penicillin, ciprofloxacin and fluconazole.…”

Lower CMV and EBV Exposure in Children With Kawasaki Disease Suggests an Under-Challenged Immune System

“…The theories about hygiene or the under-challenged immune system due to low exposure to environmental or infectious agents, have been suggested to contribute to a pathological response to a pathogen (69), which may be relevant to triggering KD in genetically susceptible children. Several studies have shown an increase of allergies in KD patients compared to the general population, which may support a link between hygiene and environmental conditions involved in the slow but progressive rise in KD incidence worldwide which can be neither caused by improved recognition and diagnostic skills of doctors nor by current laboratory tests for KD since these are not yet applicable (70)(71)(72)(73).…”