A set of proteins detected in urine by researchers at Boston Children's Hospital may prove to be the first biomarkers for Kawasaki disease, an uncommon but increasingly prevalent disease which causes inflammation of blood vessels that can lead to enlarged coronary arteries and even heart attacks in some children. If validated in more patients with Kawasaki disease, the markers could make the disease easier to diagnose and give doctors an opportunity to start treatment earlier.
The discovery was reported online by a team led by members of the Proteomics Center and the departments of Pathology and Rheumatology at Boston Children's on Dec. 20 in the journal EMBO Molecular Medicine.
While only about two in 10,000 children in the United States develop Kawasaki disease annually, the disease is on the rise both here and worldwide; in Japan the prevalence approaches one in 100 among children under the age of 5. No one knows what triggers the disease, and though it can occur at any age, it most often appears in children under 5.
Kawasaki disease is highly treatable—approximately 80 percent of children diagnosed with it require only one round of treatment—but making a diagnosis is often a significant challenge. And if it is not detected early, Kawasaki disease can have serious consequences: About 25 percent of children with untreated Kawasaki disease develop coronary artery aneurysms.
"The symptoms of Kawasaki disease, including fever, rash and enlarged lymph nodes, mimic those found in many common viral or bacterial infections in children," said Susan Kim, MD, MMSc, a rheumatologist with the Kawasaki Disease Program at Boston Children's. "The process of diagnosis includes considering a long list of possibilities. Especially in children with an incomplete presentation, a diagnosis of Kawasaki can be delayed or even missed.
"We'd like to have a test that we can use to proactively distinguish children with Kawasaki disease from those with other causes of fever," she continued. "This would allow us to start treatment much earlier and greatly reduce the risks of long-term complications."
In order to develop an effective diagnostic test, Kim worked with proteomics experts Alex Kentsis, MD, PhD, and Hanno Steen, PhD, to screen the protein content of urine from patients with Kawasaki disease using mass spectrometry and enzyme-linked immunosorbant assays. Kentsis and Steen had previously identified urine biomarkers for acute appendicitis, an effort aimed at reducing the numbers of children who either underwent unnecessary appendectomies or who had a ruptured appendix that did not show up on an imaging scan.
The team identified 190 proteins found only in the urine of children with Kawasaki disease. When validated in samples from 107 children seen at Boston Children's with suspected Kawasaki disease (53 of whom were ultimately diagnosed with it), two of the proteins—filamin C and meprin A, which are associated with injury to blood vessel and cardiac muscle cells as well as inflammation—proved to be 98 percent accurate at distinguishing children with Kawasaki disease from ones with conditions mimicking the disease. Levels of the markers also closely tracked treatment response and, in one patient, disease recurrence.
Other Kawasaki-associated markers detected in the study included proteins involved in immune activation, immune regulation and pathogen recognition.
The researchers caution that for the moment the markers are still research tools and that they are working to refine and validate the findings in a larger group of patients. "We are working with the hospital's Technology Innovation and Development Office to find corporate partners with which to develop a clinical-grade test," said Steen, who directs the Proteomics Center.
"This is very exciting and our results are very promising," said Kim. "Of course we need to validate the results in a broader cohort of patients, ideally in collaboration with other centers. We are hopeful that these findings will help us to develop a test that can help specifically and proactively detect or rule out Kawasaki in suspected patients in the future."
Boston Children's Hospital: http://www.childrenshospital.org/newsroom
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Volunteers in Sweden were tricked into thinking their bodies had vanished, and the "superpower" seemed to ease social fears
Scientists have for the first time captured how taste sensations are processed on the tongue
Researchers set hungry mosquitoes loose on identical and fraternal twins. They found that inherited genes do play a role in making you a mosquito magnet.
State education committee passes a bill banning parents exempting kids from vaccination because of "personal beliefs", as lawmakers around the world discuss similar measures
The torturous trial-and-error process of finding the best cancer drug for an individual could be a thing of the past thanks to a couple of clever devices
A flu strain deadly to chickens and turkeys is striking farms in the West and Midwest. This week, it hit an Iowa facility with millions of egg-laying hens. No one knows how it's entering houses.
Doctors, it turns out, often don't follow evidence-based guidelines. One result? Unnecessary tests. Scientists who study this contrariness think they know why.
Analysis of millions of audio files has led one US company to claim that their software can predict how a person’s voice will make a listener feel
Bird flu outbreak now spreading through Midwest poultry could head east with fall migration
A little MRI video seems to settle the decades-old debate about that loud pop of the joints: It's all about bubbles. But imagine an air bag inflating, not the bursting of a balloon.