Researchers zero in on the possible cause of Kawasaki disease

In an important discovery in infectious disease research, a team of scientists from Northwestern University has identified a possible viral cause of Kawasaki disease, the most common cause of acquired heart disease in children in developed nations.

Since 1967 when Kawasaki disease was originally described, investigators have suspected an infectious cause, but, until now, none has been identified.

The research group was led by Anne H. Rowley, M.D., professor of pediatrics and of microbiology/immunology at Northwestern University Feinberg School of Medicine and Children's Memorial Hospital.

An article describing the new findings was published in the Nov. 15 issue of the Journal of Infectious Disease.

In previous research, Rowley and colleagues showed that synthetic versions of immunoglobulin A antibodies made by children who developed Kawasaki disease bind, or attach, to spheroid structures in the bronchi, the breathing tubes in the lung. These antibodies are likely produced to combat the infectious cause of the disease.

In the current study, Rowley and co-investigators examined the spheroid structures in acute Kawasaki disease bronchi closely, using a variety of microscopic stains including the very high-powered electron microscope.

The researchers determined that the spheroid structures are inclusion bodies consisting of proteins and nucleic acids, characteristic of an infectious agent such as a virus.

Findings from the study suggest a single respiratory viral cause or closely related viral mediators as causing Kawasaki disease, entering through the respiratory route, infecting bronchi and leading to the formation of inclusion bodies in the bronchi of children with the disease.

"The virus is likely to be taken up by white blood cells in the lung and carried through the bloodstream, infecting other tissues, including the coronary artery, and leading to coronary artery aneurysms, the most important adverse outcome of Kawasaki disease," Rowley said.

Results of the study provide new insights into the cause and disease course of acute Kawasaki disease, and suggest new directions for homing in on the cause of the disease.

Rowley's collaborators on this study were Stanford T. Shulman, M.D., professor of pediatrics; Susan E. Crawford, M.D., associate professor of pathology; Pauline M. Chou, M.D., professor of pathology; and Francesca L. Garcia, Feinberg School; as well as Dr. Susan C. Baker and Linda M. Fox, Stritch School of Medicine, Loyola University; Jan M. Orenstein, M.D., George Washington University School of Medicine, Washington, D.C.; and Kei Takahashi, M.D., Toho University School of Medicine, Tokyo, Japan.

This study was supported by grants from the National Institutes of Health (KO2 HL67011 and RO1 HL63771) and the Kawasaki Disease Research Fund of Children's Memorial Hospital.

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