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Aetiological Significance of Infectious Stimuli in Kawasaki Disease

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Review

Aetiological Significance of Infectious Stimuli in Kawasaki Disease

Akihiro Nakamura et al. Front Pediatr.

Abstract

Kawasaki disease (KD) is a pediatric vasculitis syndrome that is often involves coronary artery lesions (e. g., coronary artery aneurysms). Although its causal factors and entire pathogenesis remain elusive, the available evidence indicates that the pathogenesis of KD is closely associated with dysregulation of immune responses to various viruses or microbes. In this short review, we address several essential aspects of the etiology of KD with respect to the immune response to infectious stimuli: 1) the role of viral infections, 2) the role of bacterial infections and the superantigen hypothesis, 3) involvement of innate immune response including pathogens/microbe-associated molecular patterns and complement pathways, and 4) the influence of genetic background on the response to infectious stimuli. Based on the clinical and experimental evidence, we discuss the possibility that a wide range of microbes and viruses could cause KD through common and distinct immune processes.

Keywords: Kawasaki disease; animal models; infection; pattern recognition receptors; superantigens; vasculitis.

Figures

Figure 1
Figure 1
Possible causal microorganisms of Kawasaki disease. Most of the listed microorganisms were identified on the basis of PCR or serological examinations of clinical specimens. The asterisks indicate experimental evidence from animal models, not clinical specimens.
Figure 2
Figure 2
Schematic depicting possible mechanisms of KD pathogenesis. Various infectious agents produce superantigens (SAgs) and pathogen/microbe-associated molecular patterns (PAMPs/MAMPs). SAgs non-specifically activate T cells, probably including potentially autoreactive T cells. PAMPs/MAMPs also stimulate immune cells [e.g., macrophages (Mϕ), dendritic cells (DCs), monocytes (MCs)] and endothelial cells (ECs) through cellular pattern recognition receptors (PRRs) (e.g., TLRs, NOD1, Dectin-1/-2). This stimulation up-regulates production of pro-inflammatory cytokines/chemokines and reactive oxygen/nitrogen species (ROS/NOS), leading to a systemic inflammatory reaction. On the other hand, PAMPs/MAMPs also activate the complement lectin pathway through soluble PRRs (e.g., ficolin-1, mannose binding lectin-2). Activated complement pathways can elicit inflammatory vascular damage through recruitment of innate inflammatory cells and direct injury to ECs. The extent of the inflammatory reaction is influenced by the genetic backgrounds of the individuals, resulting in a limited number of children developing KD in response to infectious stimuli.

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References

    1. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Arerugi. (1967) 16:178–222. - PubMed
    1. AHA Scientific Statement Diagnostic guidelines for Kawasaki disease. Circulation. (2001) 103:335–6. 10.1161/01.CIR.103.2.335 - DOI - PubMed
    1. Kuo H. Preventing coronary artery lesions in Kawasaki disease. Biomed J. (2017) 40:141–6. 10.1016/j.bj.2017.04.002 - DOI - PMC - PubMed
    1. Lo MS, Newburger JW. Role of intravenous immunoglobulin in the treatment of Kawasaki disease. Int J Rheum Dis. (2018) 21:64–9. 10.1111/1756-185X.13220 - DOI - PubMed
    1. Uehara R, Belay ED, Maddox RA, Holman RC, Nakamura Y, Yashiro M, et al. . Analysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan. Pediatr Infect Dis J. (2008) 27:155–60. 10.1097/INF.0b013e31815922b5 - DOI - PubMed

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