Mass spectrometry-based proteomic analysis of the human urine proteome, the entire set of proteins found in human urine, uncovered molecular markers that offer significant improvements for the diagnosis of the disease. The results are reported in a new study published in EMBO Molecular Medicine.
“There is no diagnostic test for Kawasaki disease. Currently available diagnostic markers lack the specificity and sensitivity needed for reliable detection of the disease which has motivated our decision to use proteomics to identify new, improved biomarkers,” said Susan Kim, a rheumatologist at Boston Children’s Hospital and an instructor at Harvard Medical School. “Kawasaki disease is often difficult to diagnose and is the most prevalent cause of acquired childhood heart disease in the developed world. Failure to detect it can lead to coronary artery aneurysms and in some cases death, particularly in children who are not diagnosed early enough or when the diagnosis is not considered and acted upon due to the presence of only some of the classic symptoms.”
Kawasaki disease can occur at any age but is most commonly found in children under the age of five years. The disease appears to influence the immune system in such a way that it attacks its own tissues. This leads to inflammation that can damage blood vessels, most notably around the heart. If untreated, Kawasaki disease leads to coronary artery aneurysms in up to 25% of cases.
The researchers used highly sensitive mass spectrometry techniques to profile the proteome of urine samples collected from children who had symptoms of Kawasaki disease. Several molecules were discovered that were exclusively present in the urine of patients with the disease. In particular, elevated levels of filamin C and meprin A were detected in both human blood and urine samples and show considerable potential for use as diagnostics.
Filamin C is a protein that helps maintain the structural integrity of heart and skeletal muscle. Meprin A is an enzyme that breaks down proteins and which is known to regulate the activities of other proteins linked to inflammation. Both of these markers could be used to identify patients with Kawasaki disease accurately using tests that are readily amenable for routine medical use.
“The urine proteome consists of thousands of protein molecules. Patients with Kawasaki disease have a unique urinary proteome that is distinct from the proteome observed for children with other causes of fever,” remarked Hanno Steen, director of the Proteomics Center at Boston Children’s Hospital and associate professor at Harvard Medical School. “In a group of 107 patients, we were able to distinguish children with Kawasaki disease from those with mimicking conditions much more reliably and accurately than currently available testing by measuring their levels of meprin A and filamin C in urine.” The researchers note that further validation of the diagnostic markers is needed and this work is in progress.
The researchers suggest that the development of clinical tests using these new markers may improve the accuracy of diagnosis of children with suspected Kawasaki disease and assist in the development of new treatments. For this purpose, the scientists have made the analyzed proteomes openly available at the Peptide Atlas (www.peptideatlas.org).
Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease
Alex Kentsis, Andrew Shulman, Saima Ahmed, Eileen Brennan, Michael C. Monuteaux, Young-Ho Lee, Susan Lipsett, Joao A. Paulo, Fatma Dedeoglu, Robert Fuhlbrigge, Richard Bachur, Gary Bradwin, Moshe Arditi, Robert P. Sundel, Jane W. Newburger, Hanno Steen, Susan KimRead the paper:
EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe.
Barry Whyte | EMBO
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine