Kawasaki Disease Program

Improving the Lives of Children With Kawasaki Disease

Kawasaki disease (KD) is an inflammatory condition affecting a child's eyes, lips, hands and coronary arteries. The disease is the leading cause of acquired heart disease in children in the U.S. and can lead, in rare cases, to heart attack and death. Many KD patients experience long-term coronary artery problems. The Portman Research Group is working to eradicate heart damage caused by KD.

Pursuing Better Treatments for Kawasaki Disease

The current treatment for KD is intravenous immunoglobulin (IVIG). Immunoglobulin consists of concentrated antibodies that have been extracted from donated blood. Infusing this product into KD patients can significantly reduce their risk of certain heart problems. But IVIG is effective in only 70% to 80% of cases. Approximately 20% to 25% of patients treated with IVIG have recurrent or persistent fever and inflammation, and these patients are at especially high risk for coronary artery disease. The Portman group is developing ways to improve outcomes for children treated with IVIG.

Dr. Portman and his colleagues made a key genetic discovery about why IVIG isn't effective in some patients. It is widely believed that IVIG works by binding to specific molecules - called FcGamma receptors, or FCGRs - on certain types of blood or inflammatory cells. Portman's team found that some patients have variations in the genes that regulate FCGRs, and that these variations lead to abnormal or mutated FCGRs that can't properly bind with the IVIG.

The lab is building on this finding through a study that collects blood and saliva samples from hundreds of KD patients. By analyzing these patients' genes, the study is searching for further clues on how genetic variations influence a patient's response to IVIG.

The Portman team made another potentially pivotal finding through a pilot study that found that when KD patients were treated with a combination of IVIG and the drug etanercept (commonly known as Enbrel), they had no recurrent fever and no new coronary artery inflammation. Now the lab is leading an FDA-sponsored clinical trial, which is taking place at six hospitals in the U.S. and Canada, to validate these results. Etanercept has been approved by the FDA as a treatment for rheumatoid arthritis and other inflammatory conditions, and the group's clinical trial could lay the foundation for using the drug in KD patients too.

Investigating Kawasaki Disease's Causes

While KD's causes are not understood, Portman developed an intriguing hypothesis that eating soy products could influence a child's risk for KD. This could help explain why the disease is unusually common in Asian populations, particularly in Japanese children.

Soybeans and soy products are the richest sources of isoflavones, a plant hormone that resembles human estrogen. For many children, the earliest significant dietary exposure to isoflavones comes through breastmilk/chestmilk or soy-based infant formulas. Portman hypothesizes that one of these isoflavones, called genistein, may limit how FcGamma receptors function. This could impair children's immune systems and make them more susceptible to KD.

Portman outlined this theory in a recent paper in Pediatric Research. The paper explains how Portman and his colleagues analyzed data on soy consumption in thousands of Caucasian, Native Hawaiian and Japanese subjects. He compared this data with KD's incidence in Hawaiian populations. The data suggest that soy consumption is associated with a higher risk of Kawasaki disease among children under age 18.

The Portman Research Group is now pursuing a case-controlled study that analyzes soy consumption among children of different ethnic backgrounds in the U.S.

Philanthropy Accelerates Research

Portman's group is making dramatic advancements toward improving the lives of children with Kawasaki disease. This progress wouldn't be possible without private donations, which fund innovative pilot studies and make up for shortfalls in grants from federal agencies and private foundations. The KD KIDS Guild was recently established to solicit financial support for this research. To learn more about supporting the guild, email us. You can also donate online.

"Funding from private philanthropy gave me money to identify the genes that create susceptibility to Kawasaki disease. Because of this support, we are very close to finding a more effective treatment for the disease."

Dr. Michael Portman