A diagnostic algorithm combining clinical and molecular data distinguishes Kawasaki disease from other febrile illnesses

Background Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kaw...

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Published inBMC medicine Vol. 9; no. 1; p. 130
Main Authors Ling, Xuefeng B, Lau, Kenneth, Kanegaye, John T, Pan, Zheng, Peng, Sihua, Ji, Jun, Liu, Gigi, Sato, Yuichiro, Yu, Tom TS, Whitin, John C, Schilling, James, Burns, Jane C, Cohen, Harvey J
Format Journal Article
LanguageEnglish
Published London BioMed Central 06.12.2011
BioMed Central Ltd
BMC
Subjects
Adult
Algorithms
Area Under Curve
Biomarkers
Biomarkers - blood
Biomarkers - metabolism
Biomarkers - urine
Biomedicine
Blood
Care and treatment
Children & youth
Colleges & universities
Confidence intervals
Coronary vessels
Data mining
Development and progression
Diagnosis
Diagnosis, Computer-Assisted - methods
Diagnosis, Differential
Discriminant analysis
Female
Fever
Fever - blood
Fever - diagnosis
Fever - genetics
Fever - urine
Fourier transforms
Gene expression
Gene Expression Profiling - methods
Genetic aspects
Hospitals
Human subjects
Humans
Kawasaki disease
Male
Medicine
Medicine & Public Health
Middle Aged
Mucocutaneous Lymph Node Syndrome - blood
Mucocutaneous Lymph Node Syndrome - diagnosis
Mucocutaneous Lymph Node Syndrome - genetics
Mucocutaneous Lymph Node Syndrome - urine
Multivariate Analysis
Pediatrics
Proteinuria - blood
Proteinuria - diagnosis
Proteinuria - urine
Proteomics - methods
Research Article
ROC Curve
Transcriptome
Veins & arteries
United States
Systemic Juvenile Idiopathic Arthritis
Coronary Artery Aneurysm
Kawasaki Disease
Kawasaki Disease Patient
Blood Cell Type
Online AccessGet full text
ISSN1741-7015
1741-7015
DOI10.1186/1741-7015-9-130

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Abstract Background Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment. Methods Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls. Results Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease. Conclusions A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.
AbstractList Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment. Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls. Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease. A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.
Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment.BACKGROUNDKawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment.Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls.METHODSUrine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls.Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease.RESULTSComparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease.A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.CONCLUSIONSA hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.
Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment. Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls. Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease. A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.
Abstract Background: Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment. Methods: Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls. Results: Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease. Conclusions: A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.
BACKGROUND: Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment. METHODS: Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls. RESULTS: Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease. CONCLUSIONS: A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.
Background Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign conditions of childhood. The etiology remains unknown and there is no specific laboratory-based test to identify patients with Kawasaki disease. Treatment to prevent the complication of coronary artery aneurysms is most effective if administered early in the course of the illness. We sought to develop a diagnostic algorithm to help clinicians distinguish Kawasaki disease patients from febrile controls to allow timely initiation of treatment. Methods Urine peptidome profiling and whole blood cell type-specific gene expression analyses were integrated with clinical multivariate analysis to improve differentiation of Kawasaki disease subjects from febrile controls. Results Comparative analyses of multidimensional protein identification using 23 pooled Kawasaki disease and 23 pooled febrile control urine peptide samples revealed 139 candidate markers, of which 13 were confirmed (area under the receiver operating characteristic curve (ROC AUC 0.919)) in an independent cohort of 30 Kawasaki disease and 30 febrile control urine peptidomes. Cell type-specific analysis of microarrays (csSAM) on 26 Kawasaki disease and 13 febrile control whole blood samples revealed a 32-lymphocyte-specific-gene panel (ROC AUC 0.969). The integration of the urine/blood based biomarker panels and a multivariate analysis of 7 clinical parameters (ROC AUC 0.803) effectively stratified 441 Kawasaki disease and 342 febrile control subjects to diagnose Kawasaki disease. Conclusions A hybrid approach using a multi-step diagnostic algorithm integrating both clinical and molecular findings was successful in differentiating children with acute Kawasaki disease from febrile controls.
ArticleNumber 130
Audience Academic
Author Burns, Jane C
Kanegaye, John T
Ji, Jun
Lau, Kenneth
Sato, Yuichiro
Schilling, James
Pan, Zheng
Ling, Xuefeng B
Whitin, John C
Liu, Gigi
Yu, Tom TS
Cohen, Harvey J
Peng, Sihua
AuthorAffiliation 1 Department of Pediatrics, Stanford University, Stanford, CA 94305, USA
2 Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA
4 Amgen Inc, South San Francisco, CA 94080, USA
3 Rady Children's Hospital San Diego, San Diego, CA 92123, USA
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/22145762$$D View this record in MEDLINE/PubMed
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COPYRIGHT 2011 BioMed Central Ltd.
2011 Ling et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright ©2011 Ling et al; licensee BioMed Central Ltd. 2011 Ling et al; licensee BioMed Central Ltd.
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– notice: COPYRIGHT 2011 BioMed Central Ltd.
– notice: 2011 Ling et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
– notice: Copyright ©2011 Ling et al; licensee BioMed Central Ltd. 2011 Ling et al; licensee BioMed Central Ltd.
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Issue 1
Keywords Systemic Juvenile Idiopathic Arthritis
Coronary Artery Aneurysm
Kawasaki Disease
Kawasaki Disease Patient
Blood Cell Type
Language English
License This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Snippet Background Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic...
Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic other benign...
Background Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic...
Abstract Background: Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that...
BACKGROUND: Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can mimic...
Abstract Background Kawasaki disease is an acute vasculitis of infants and young children that is recognized through a constellation of clinical signs that can...
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SubjectTerms Adult
Algorithms
Area Under Curve
Biomarkers
Biomarkers - blood
Biomarkers - metabolism
Biomarkers - urine
Biomedicine
Blood
Care and treatment
Children & youth
Colleges & universities
Confidence intervals
Coronary vessels
Data mining
Development and progression
Diagnosis
Diagnosis, Computer-Assisted - methods
Diagnosis, Differential
Discriminant analysis
Female
Fever
Fever - blood
Fever - diagnosis
Fever - genetics
Fever - urine
Fourier transforms
Gene expression
Gene Expression Profiling - methods
Genetic aspects
Hospitals
Human subjects
Humans
Kawasaki disease
Male
Medicine
Medicine & Public Health
Middle Aged
Mucocutaneous Lymph Node Syndrome - blood
Mucocutaneous Lymph Node Syndrome - diagnosis
Mucocutaneous Lymph Node Syndrome - genetics
Mucocutaneous Lymph Node Syndrome - urine
Multivariate Analysis
Pediatrics
Proteinuria - blood
Proteinuria - diagnosis
Proteinuria - urine
Proteomics - methods
Research Article
ROC Curve
Transcriptome
Veins & arteries
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Title A diagnostic algorithm combining clinical and molecular data distinguishes Kawasaki disease from other febrile illnesses
URI https://link.springer.com/article/10.1186/1741-7015-9-130
https://www.ncbi.nlm.nih.gov/pubmed/22145762
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http://dx.doi.org/10.1186/1741-7015-9-130
https://pubmed.ncbi.nlm.nih.gov/PMC3251532
https://doaj.org/article/58a15840a71a44cca549b405d692981f
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