Autoimmune Aspects of Kawasaki Disease

Abstract

Kawasaki disease (KD) is classified as a medium-sized vasculitis of systemic vasculitis syndrome characterized by hypercytokinemia. Although the etiology of KD remains unidentified, epidemiological features point to the role of infection and genetic predisposition. Recent studies revealed endothelial damage and resultant thrombin generation, as well as B-cell activation during the acute phase of KD. Several anti-endothelial cell autoantibodies (AECAs) have been identified in KD patients. Taken together with the recently developed concept of immunothrombosis, a potential pathogenic mechanism for KD emerges. First, some polyclonal antibodies generated against invading microorganisms would exhibit cross-reactivity toward endothelial cell components and become dominant during affinity maturation. AECA binding to endothelial cells would cause endothelial activation or damage, with proinflammatory cytokine release, fostering a hypercoagulable state by leukocyte activation by proinflammatory cytokines. This, in turn, would lead to coronary artery lesions. KD vasculitis might be initiated upon AECA binding 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 ultra-large von Willebrand factor (VWF) released by endothelial cells, would cause platelet-driven arterial thrombosis. Autoimmunity-associated thrombosis initiated by AECA binding 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 facilitate a better understanding of KD and further promote early and accurate diagnosis, which remains challenging.

Association between Kawasaki Disease and Prenatal Exposure to Ambient and Industrial Air Pollution: A Population-Based Cohort Study

“…Inflammatory mechanisms are common features of Kawasaki disease and air pollution and are also involved in preexisting and gestational diabetes, possibly explaining the enhanced susceptibility in children with a maternal history of diabetes (Zhao et al 2019;O'Neill et al 2007;Radaelli et al 2003). Furthermore, gestational diabetes has been associated with a greater risk of type 1 diabetes (Blotsky et al 2019), which is an autoimmune disorder, as is Kawasaki disease (Sakurai 2019). Further research will be needed to determine whether different variants of diabetes can affect the association between air pollution and Kawasaki disease.…”

Antibodies and Immunity During Kawasaki Disease

“…A role for B cells could imply a significant autoimmune component in KD (170). Self-antigen responses to a variety of targets have actually been well-described in KD.…”

“…Recently, the autoimmune considerations in KD have been reviewed (170). The case report of anti-B cell monoclonal antibody success was proposed by the authors to be due to the downregulation of such an anti-endothelial invasive effect (140).…”

Utilizing Network Pharmacology to Explore the Possible Mechanism of CoptidisRhizoma in Kawasaki Disease

“…However, up to 15-20% of patients with Kawasaki disease do not respond to IVIG treatment and have an increased rate of CAA [6]. Yet, the underlying mechanisms of KD remain unclear and it may be related to unbalanced autoimmunity and genetic susceptibility [7]. It is important to systematically elucidate the mechanism of the disease and search for more effective agents against it.…”