Innate immune responses following Kawasaki disease and toxic shock syndrome

Abstract

The pathogenesis of Kawasaki disease (KD) remains unknown and there is accumulating evidence for the importance of the innate immune system in initiating and mediating the host inflammatory response. We compared innate immune responses in KD and toxic shock syndrome (TSS) participants more than two years after their acute illness with control participants to investigate differences in their immune phenotype. Toxic shock syndrome shares many clinical features with KD; by including both disease groups we endeavoured to explore changes in innate immune responses following acute inflammatory illnesses more broadly. We measured the in vitro production of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10 following whole blood stimulation with toll-like receptor and inflammasome ligands in 52 KD, 20 TSS, and 53 control participants in a case-control study. Analyses were adjusted for age, sex, and unstimulated cytokine concentrations. Compared to controls, KD participants have reduced IL-1ra production in response to stimulation with double stranded RNA (geometric mean ratio (GMR) 0.37, 95% CI 0.15, 0.89, p = 0.03) and increased IL-6 production in response to incubation with Lyovec™ (GMR 5.48, 95% CI 1.77, 16.98, p = 0.004). Compared to controls, TSS participants have increased IFN-γ production in response to peptidoglycan (GMR 4.07, 95% CI 1.82, 9.11, p = 0.001), increased IL-1β production to lipopolysaccharide (GMR 1.64, 95% CI 1.13, 2.38, p = 0.01) and peptidoglycan (GMR 1.61, 95% CI 1.11, 2.33, p = 0.01), and increased IL-6 production to peptidoglycan (GMR 1.45, 95% CI 1.10, 1.92, p = 0.01). Years following the acute illness, individuals with previous KD or TSS exhibit a pro-inflammatory innate immune phenotype suggesting a possible underlying immunological susceptibility or innate immune memory.

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.…”

Aetiological Significance of Infectious Stimuli in Kawasaki Disease

“…The aetiological mechanism of KD remains unclear and the causal factors are also unknown (6). Although there is no definitive evidence that KD is an infectious disease, recent studies support the view that a dysregulated immune response to a variety of infectious stimuli is likely to contribute to KD pathogenesis (6,7). Based on these studies, this short review explores the possible relationship between KD and the immune response to various infectious agents (Figure 1).…”

The IL-1B Gene Polymorphisms rs16944 and rs1143627 Contribute to an Increased Risk of Coronary Artery Lesions in Southern Chinese Children with Kawasaki Disease

“…Many studies have shown that immune activation and secretion of various cytokines play a key role in the pathogenesis of KD by mediating the imbalance of proinflammatory and anti-inflammatory responses. A variety of proinflammatory and anti-inflammatory cytokines have been reported to increase significantly during acute KD, such as IL-1 , TNF-α , IL-6 , IL-8 , and IL-10 [12–14]. These proinflammatory cytokines induce endothelial cell apoptosis, which is the cause of vascular endothelial injury in KD and has been implicated in the development of the disease [15–17].…”