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Open Access Research article

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

Xuefeng B Ling1, Kenneth Lau1, John T Kanegaye23, Zheng Pan4, Sihua Peng1, Jun Ji1, Gigi Liu1, Yuichiro Sato2, Tom TS Yu1, John C Whitin1, James Schilling1, Jane C Burns2 and Harvey J Cohen1*

Author affiliations

1 Department of Pediatrics, Stanford University, Stanford, CA 94305, USA

2 Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA

3 Rady Children's Hospital San Diego, San Diego, CA 92123, USA

4 Amgen Inc, South San Francisco, CA 94080, USA

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Citation and License

BMC Medicine 2011, 9:130  doi:10.1186/1741-7015-9-130

Published: 6 December 2011

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.