Susceptibility Loci to Coronary Arteritis in Animal Model of Kawasaki Disease Induced with Candida albicans‐Derived Substances

Abstract

We have established an animal model of coronary arteritis which is histopathologically similar to that observed in cases of Kawasaki disease (KD), is a well‐known childhood vasculitis syndrome. Coronary arteritis in this mouse model has been induced by intraperitoneal injection of Candida albicans‐derived substances (CADS). Arteritis varied by mouse strain with the highest incidence by 71.1% (27/38) found in C3H/HeN mice, but absent in CBA/JN mice (0%, 0/27), suggesting association of genomic background to develop the disease. The present study aims to elucidate the susceptibility loci associated with coronary arteritis by using this animal model. The association of the onset of arteritis with polymorphic microsatellite markers between the two strains was examined using one hundred and fifteen of N1 backcross progeny [(CBA×C3H)F1×C3H]. Based on our analysis, arteritis‐susceptibility loci with suggestive linkage were mapped on D1Mit171 and D1Mit245 (map position 20.2 cM) on chromosome 1 (P=0.0019). These loci include several kinds of inflammatory cytokine receptors, such as interleukin 1 receptor and tumor necrosis factor receptor. We also found the cytokine response against CADS, levels of inflammatory cytokines interleukin‐1β, tumor necrosis factor‐α, and interleukin‐6 in sera increased within 24 hr after CADS injection. Our results may indicate based on genomics that ligand‐receptor interaction between these inflammatory cytokines and the receptors of these cytokines may affect the onset of arteritis.

Tropospheric winds from northeastern China carry the etiologic agent of Kawasaki disease from its source to Japan

“…The presence of Candida sequences is intriguing in light of murine models of coronary arteritis based on exposure to Candida glucans comprising mannose, β-1,3-glucan and β-1,6-glucan. Vulnerability to disease varies by mouse strain and is associated with elevated levels of IL-6, TNF-α, and IFN-γ (21,22). Similar to KD, vasculitis can be abrogated by use of i.v.…”

Administration of human immunoglobulin suppresses development of murine systemic vasculitis induced with Candida albicans water-soluble fraction: an animal model of Kawasaki disease

“…We used that model to carry out various studies [6,7,13] and showed that administration of CADS induced systemic vasculitis, including coronary arteritis, in about 70% of mice. This model is considered to be highly useful as an experimental model of KD, especially in view of the fact that it induces granulomatous inflammation of the coronary arteries [7].…”

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Large Vessel Vasculitis and Kawasaki Disease in Japan

“…In an additional study on Candida -derived agents, C. albicans watersoluble fraction (CAWS) induced severe vasculitis at a higher rate of incidence than CADS in many mouse strains, and there are reports on this valuable animal model system in research on systemic immune responses and inflammatory vascular disease [77][78][79] . The CAWSinduced coronary arteritis is a good model for the histological observation of KD.…”