Lower CMV and EBV Exposure in Children With Kawasaki Disease Suggests an Under-Challenged Immune System

Abstract

Background: Kawasaki Disease (KD) is a pediatric vasculitis of which the pathogenesis is unclear. The hypothesis is that genetically pre-disposed children develop KD when they encounter a pathogen which remains most often unidentified or pathogen derived factors. Since age is a dominant factor, prior immune status in children could influence their reactivity and hence the acquisition of KD. We hypothesized that systemic immune responses early in life could protect against developing KD. With this study we tested whether the incidence of previous systemic cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection is lower in children with KD compared to healthy age-matched controls.Methods and Results: We compared 86 KD patients with an age-matched control group regarding CMV and EBV VCA IgG measurements (taken before or 9 months after IVIG treatment). We found that both CMV and EBV had an almost 2-fold lower seroprevalence in the KD population than in the control group.Conclusions: We suggest that an under-challenged immune system causes an altered immune reactivity which may affect the response to a pathological trigger causing KD in susceptible children.

Emerging evidence of microbial infection in causing systematic immune vasculitis in Kawasaki disease

“…Notably, a case of Kawasaki disease triggered by EBV virus infection was found to be complicated with familial Mediterranean fever ( Maggio et al, 2019 ). Moreover, the prevalence of EBV in KD children was significantly lower during the early stage ( van Stijn et al, 2020 ), and deoxyuridine 5′-triphosphate nucleotide hydrolase (dUTPase), a pathogen nonstructural protein encoded by EBV, can stimulate monocyte-derived macrophages through Toll-like receptor 2-dependent signaling transduction ( Ariza et al, 2009 ), suggesting that DUTPase could be used as a potential target for drug development against EBV infection and KD treatment.…”