Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease
Open Access
- 20 December 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 5 (2), 210-220
- https://doi.org/10.1002/emmm.201201494
Abstract
Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Absence of definitive diagnostic markers limits the accuracy of clinical evaluations of suspected KD with significant increases in morbidity. In turn, incomplete understanding of its molecular pathogenesis hinders the identification of rational targets needed to improve therapy. We used high‐accuracy mass spectrometry proteomics to analyse over 2000 unique proteins in clinical urine specimens of patients with KD. We discovered that urine proteomes of patients with KD, but not those with mimicking conditions, were enriched for markers of cellular injury such as filamin and talin, immune regulators such as complement regulator CSMD3, immune pattern recognition receptor muclin, and immune cytokine protease meprin A. Significant elevations of filamin C and meprin A were detected in both the serum and urine in two independent cohorts of patients with KD, comprised of a total of 236 patients. Meprin A and filamin C exhibited superior diagnostic performance as compared to currently used markers of disease in a blinded case‐control study of 107 patients with suspected KD, with receiver operating characteristic areas under the curve of 0.98 (95% confidence intervals [CI] of 0.97–1 and 0.95–1, respectively). Notably, meprin A was enriched in the coronary artery lesions of a mouse model of KD. In all, urine proteome profiles revealed novel candidate molecular markers of KD, including filamin C and meprin A that exhibit excellent diagnostic performance. These disease markers may improve the diagnostic accuracy of clinical evaluations of children with suspected KD, lead to the identification of novel therapeutic targets, and allow the development of a biological classification of Kawasaki disease.This publication has 45 references indexed in Scilit:
- Long-Term Prognosis of Patients With Kawasaki Disease Complicated by Giant Coronary AneurysmsCirculation, 2011
- Urinary Proteomic Biomarkers in Coronary Artery DiseaseMolecular & Cellular Proteomics, 2008
- Randomized Trial of Pulsed Corticosteroid Therapy for Primary Treatment of Kawasaki DiseaseThe New England Journal of Medicine, 2007
- Discovery of Urinary BiomarkersMolecular & Cellular Proteomics, 2006
- Analysis of Human Proteome Organization Plasma Proteome Project (HUPO PPP) reference specimens using surface enhanced laser desorption/ionization‐time of flight (SELDI‐TOF) mass spectrometry: Multi‐institution correlation of spectra and identification of biomarkersProteomics, 2005
- Differential gene expression of S100 protein family in leukocytes from patients with Kawasaki diseaseEuropean Journal of Pediatrics, 2005
- Filamin C accumulation is a strong but nonspecific immunohistochemical marker of core formation in muscleJournal of the Neurological Sciences, 2003
- Nationwide survey of Kawasaki disease and acute rheumatic feverThe Journal of Pediatrics, 1991
- Clinical and epidemiologic characteristics of patients referred for evaluation of possible Kawasaki diseaseThe Journal of Pediatrics, 1991
- Variable expression of Lactobacillus casei cell wall-induced coronary arteritis: An animal model of Kawasaki's disease in selected inbred mouse strainsClinical Immunology and Immunopathology, 1988