Kawasaki disease: a matter of innate immunity

Abstract

SummaryKawasaki disease (KD) is an acute systemic vasculitis of childhood that does not have a known cause or aetiology. The epidemiological features (existence of epidemics, community outbreaks and seasonality), unique age distribution and clinical symptoms and signs of KD suggest that the disease is caused by one or more infectious environmental triggers. However, KD is not transmitted person-to-person and does not occur in clusters within households, schools or nurseries. KD is a self-limited illness that is not associated with the production of autoantibodies or the deposition of immune complexes, and it rarely recurs. Regarding the underlying pathophysiology of KD, innate immune activity (the inflammasome) is believed to play a role in the development of KD vasculitis, based on the results of studies with animal models and the clinical and laboratory findings of KD patients. Animal studies have demonstrated that innate immune pathogen-associated molecular patterns (PAMPs) can cause vasculitis independently of acquired immunity and have provided valuable insights regarding the underlying mechanisms of this phenomenon. To validate this concept, we recently searched for KD-specific PAMPs and identified such molecules with high specificity and sensitivity. These molecules have structures similar to those of microbe-associated molecular patterns (MAMPs), as shown by liquid chromatography-tandem mass spectrometry. We propose herein that KD is an innate immune disorder resulting from the exposure of a genetically predisposed individual to microbe-derived innate immune stimulants and that it is not a typical infectious disease.

Aetiological Significance of Infectious Stimuli in Kawasaki Disease

“…PAMPs and MAMPs are recognized by a type of cellular or soluble receptors, which are designated pattern recognition receptors (PRRs) (e.g., TLRs) to trigger innate immune responses, including the production of inflammatory cytokines through intracellular signaling pathways. A possible implication of these PAMPs or MAMPs in KD has been demonstrated in mouse models and more recently in clinical specimens from KD patients (78,79).…”

Adjuvant herbal therapy for targeting susceptibility genes to Kawasaki disease: An overview of epidemiology, pathogenesis, diagnosis and pharmacological treatment of Kawasaki disease

“…It was proposed by Lee et al that the immunopathogenesis of KD is based on a "protein homeostasis system" that controls the pathogenic toxic proteins which spread and bind to endothelial cells of coronary arteries, with the involvement of non-specific T cells and non-specific antibodies to produce various cytokines contributing to endothelial cell injury (Lee et al, 2012a). While both the innate and acquired systems are activated after pathogen infection, clinical and laboratory studies have found that the occurrence of KD is related to the activation of the innate immune system (Hara et al, 2016). Lori Broderick et al reported 4 cases of KD with the reoccurrence of inflammatory clinical symptoms similar to those in "recurrent fever syndrome" existed in febrile disease due to the dysregulation of innate immune system (Broderick et al, 2011).…”

Application of Extracellular Vesicles Proteomics to Cardiovascular Disease: Guidelines, Data Analysis, and Future Perspectives

“…It is noteworthy that the innate immune system has an important role during the acute phase of KD . There are some complement‐related proteins such as C3, C4 and complement factor H (CFH), overlapped.…”