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.
It's all fun and games until someone dislocates a knee, wets himself or has a stroke
Use of synthetic drugs, like bath salts, by young people continues to decline across the nation, according to a study by the University of Michigan.
Researchers are struggling with how to balance the benefits and risks of genetic experiments that can give viruses new talents for causing infections.
For all the medicine they provide at this center, physicians and staff from Doctors Without Borders spend as much time encouraging the patients to eat, drink, and keep fighting. Every patient gets a standard regimen of antibiotics, paracetemol and other pain medications, vitamins, oral rehydration therapy or intravenous fluids. Drugs can control nausea for those who need them; everyone gets antimalarials.
Dengue sickens millions of people each year, and there's no cure. Now scientists have found powerful antibodies that stop the virus. Their discovery offers a road map to develop a simple vaccine.
British doctors make the case for playing music during an operation
Doughnuts? No thank you. An edible powder made from stuff our gut bacteria excrete can stop people gaining weight when taken daily
While the US intelligence agency brutalised detainees, evidence that torture was counterproductive was staring it in the face, says Michael Bond
Aggressive tactics and discriminatory policies have brought the US police system to a deadly impasse
Kids who are given a moral reason to tell the truth tend to do so more often