Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease.
Bottom Line: 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.Notably, meprin A was enriched in the coronary artery lesions of a mouse model of KD.
Affiliation: Division of Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.Show MeSH
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Mentions: Candidate diagnostic markers of KD were identified based on the analysis of 15 specimens collected at the onset of the study and chosen based on availability: 6 KD specimens (3 without and 3 with coronary artery dilatation), 6 non-KD specimens (2 with non-specific viral syndromes, 3 with adenovirus, and 1 with pyelonephritis), and 3 matched specimens collected from patients with KD 1 month following complete response to treatment (convalescent KD). This analysis identified 2131 unique proteins, with the tissue and physical origin of the aggregate urine proteomes similar to previous studies (Kentsis et al, 2009). Analysis of the three comparison groups led to the identification of more than 190 proteins in the urine of patients with KD, but not in any of the patients without KD or in those whose KD had resolved completely (Supporting Information Table 1). We analysed the abundance of candidate KD markers to identify those that are most enriched in patients with KD, ranking them in order of relative abundance and prevalence (Fig 1). The identified markers include a variety of proteins associated with endothelial and myocardial cell injury such as filamin and titin, and immune regulators such as DMBT1 and meprin A. Many of the detected markers are high molecular weight proteins, which are probably enriched in the urine of patients with KD as processed and/or truncated proteins, as confirmed for meprin A and filamin C by Western immunoblotting (Fig 1A). The discovered proteomes are provided in Supporting Information Table 2 (processed data), and the raw data, in accordance with the MIAPE standard, and are openly available at Peptide Atlas (http://www.peptideatlas.org).
Affiliation: Division of Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.