The etiology of Kawasaki disease: a superantigen-mediated process

Abstract

Kawasaki disease (KD) is the most common cause of vasculitis affecting children. Although the inflammatory response is found in medium and small vessels throughout the body, the most common site of end organ damage is the coronary arteries. Kawasaki disease is now recognized as the leading cause of acquired heart disease in children in the developed world. Despite appropriate therapy with intravenous gammaglobulin, affected children continue to develop coronary artery lesions. Many gaps exist in our knowledge of the etiology and pathogenesis of Kawasaki disease making improvements in therapy difficult. Despite the widely held belief that Kawasaki disease is an infectious disease, its etiology remains elusive. Many different etiologic agents ranging from bacteria to viruses have been identified, but no one causative agent has been consistently found. The etiology debate has centered around the mechanism of immune activation: conventional antigen versus superantigen. Superantigens (SAGs) encompass a family of proteins that are able to cause dramatic immune activation that is T cell dependent. A variety of microbes have the ability to produce superantigens and many of these have been implicated in the pathogenesis of human disease including Kawasaki disease. In this article, I will review the evidence pointing to superantigens as culprits in the immunopathogenesis of Kawasaki disease and provide a unifying hypothesis to account for the ostensibly opposing data used by proponents of both the conventional antigen and superantigen theories.