Autoimmune Aspects of Kawasaki Disease

Kawasaki disease (KD) is a vasculitis that is part of systemic vasculitis syndrome. It affects medium-sized vessels and is characterized by hypercytokinemia. Although the etiology of KD remains unidentified, epidemiological features point to the role of infection and genetic predisposition. Recent studies on KD revealed endothelial damage and resultant thrombin generation, as well as B-cell activation during the acute phase. Several antiendothelial cell autoantibodies (AECAs) have been identified in KD patients. Analysis of this phenomenon together with the recently developed concept of immunothrombosis reveals a potential pathogenic mechanism for KD. First, polyclonal antibodies generated against invading microorganisms would exhibit cross-reactivity toward endothelial cell components and become dominant during affinity maturation. Binding of AECAs to endothelial cells would cause endothelial activation or damage, with proinflammatory cytokine release, thus fostering a hypercoagulable state resulting from leukocyte activation by proinflammatory cytokines. This, in turn, would lead to coronary artery lesions. KD vasculitis might be initiated upon binding of AECAs to the vasa vasorum and progress to panvasculitis and a vulnerable vessel wall, resulting in an aneurysm. The aneurysm would cause flow recirculation and alteration of wall shear stress. Consequently, platelets activated by shear stress, along with ultralarge von Willebrand factor (VWF) released by endothelial cells, would cause platelet-driven arterial thrombosis. Autoimmunity-associated thrombosis initiated by binding of AECAs to endothelial cells might play a major role in the pathogenesis of certain subtypes of KD. The notion of KD consisting of subtypes, the major one of which is AECA-associated vasculitis, will help improve our understanding of KD and further promote early and accurate diagnosis, which remains challenging.