Urine Proteomics May Have Potential in Diagnosis of Kawasaki Disease

Urine is well recognized as a rich source of systemic proteins and with far less complexity and ease of collection when compared to serum. Could urine proteomics then provide an opportunity for diagnosing Kawasaki disease?¹

Kawasaki disease is a rare childhood condition, involving inflammation of a child’s blood vessels. Diagnosis relies on patient presentation of a range of symptoms, including a high fever, swelling in the hands and feet, bloodshot eyes, and red mucous membranes. However, the symptoms associated with Kawasaki disease mimic many other febrile childhood diseases.² There is no specific test for Kawasaki disease, and its etiology remains unknown.³ The accuracy of diagnosis could be significantly improved with a definitive set of diagnostic tools. Kentsis et al.⁴ have proposed a set of biomarkers, defined using urinary proteomics, as having potential diagnostic validity.

170 children who presented with symptoms of Kawasaki disease were enrolled in the study. Of the children enrolled, 53 received a final diagnosis of Kawasaki disease. There were 190 proteins in the urine of patients with Kawasaki disease that did not occur in patients without Kawasaki disease. Those proteins that were most enriched in Kawasaki disease were considered more closely as potential biomarkers. These proteins included proteins associated with endothelial and myocardial cell injury, such as filamin and titin, and immune regulators, such as DMBT1 and meprin A. A hybrid linear ion trap-Fourier transform ion cyclotron resonance mass spectrometer (Thermo Scientific) was used to process the individual urine protein fractions, and the 200 most intense peaks were extracted and searched against the human International Protein Index database. Urinary proteomics identified, a set of signatures of distinct biological processes associated with Kawasaki disease. In particular, meprin a and filamin c were selected for validation based on the biological processes they are believed to be involved in: meprin a, for its role in the activation and degradation of inflammatory cytokines implicated in the pathogenesis of Kawasaki disease, and filamin c, for its relationship to the myocarditis that accompanies Kawasaki disease.

One of the ongoing challenges in proteomics has been its translation back into a clinical setting. Kentsis et al. have taken the results from their urine proteomics study a step further. Not only has their study used proteomics technology to identify a reliable set of biomarkers, but they have defined a test that is accessible in a clinical setting using available ELISAs that can be used to identify these biomarkers and, thus, reliably diagnose Kawasaki disease.

References

1. Adachi, J., et al. (2006) ‘The human urinary proteome contains more than 1500 proteins, including a large proportion of membrane proteins‘ Genome Biology, 7 (9), R80.

2. Baker, A.L., et al. (2009) ‘Associated symptoms in the ten days before diagnosis of Kawasaki disease‘, Journal of Pediatrics, 154 (4), (pp. 592-595)

3. Kawasaki Disease, PubMed Health, http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001984/

4. Kentsis, A., et al. (2012) ‘Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease‘, EMBO Molecular Medicine, 5 (2), (pp. 210–220)