epiglucan and Mucocutaneous-Lymph-Node-Syndrome

Kawasaki disease (KD) is an inflammatory disease that was identified by Professor Tomisaku Kawasaki in 1961. Candida albicans-derived substances, such as C. albicans water-soluble fraction (CAWS) , induce coronary arteritis similar to KD in mice. CAWS functions as a pathogen-associated molecular pattern (PAMP) by acting as a ligand for dectin-2. A gut-associated immunological system has developed specifically to segregate advantageous and detrimental stimuli, and the microbial flora has been found to markedly affect the development and severity of diseases. We herein investigated whether diet affects the onset and progression of CAWS vasculitis in mice. A standard diet, CE-2, and chemically defined diet, AIN93G, which is free of β-glucan, were used. Although all mice administered with CAWS died, the mean number of survival days was smaller in the AIN93G group because vasculitis was induced earlier than in the CE-2 group. Bacteroides, which are inflammatory flora, were enriched in the microbial flora of the AIN93G group. The results of the present study suggest that diet quality affects not only microbial flora changes, but also the progression of systemic disease.

Topics: Animals; Bacteroides; beta-Glucans; Candida albicans; Diet; Disease Progression; Food; Gastrointestinal Microbiome; Gastrointestinal Tract; Lectins, C-Type; Ligands; Male; Mice, Inbred DBA; Mucocutaneous Lymph Node Syndrome; Solubility; Subcellular Fractions; Vasculitis; Water

Kawasaki disease (KD) is an acute vasculitis syndrome of unknown aetiology in children. The administration of Candida cell wall antigens induced KD-like coronary vasculitis in mice. However, the responses of KD patients to Candida cell wall antigen are unknown. In this study, we examined the response of KD patients to β-glucan (BG), one of the major fungal cell wall antigens, by measuring the anti-BG titre. In KD patients, the anti-C. albicans cell wall BG titre was higher than that in normal children. The anti-BG titre was also higher in KD patients compared to children who served as control subjects. The efficacy of intravenous immunoglobulin (IVIG) therapy in KD is well established. We categorized the KD patients into three groups according to the therapeutic efficacy of intravenous immunoglobulin (IVIG) and compared the anti-BG titre among these groups. Anti-BG titres were similar in the control group and the non-responsive group. In the fully responsive group, the anti-BG titre showed higher values than those in the normal children. This study demonstrated clinically that KD patients have high antibody titres to Candida cell wall BG, and suggested the involvement of Candida cell wall BG in the pathogenesis of KD. The relationship between IVIG therapy and anti-BG titre was also shown. These results provide valuable insights into the therapy and diagnosis of KD.

Topics: Antibodies, Fungal; beta-Glucans; Biomarkers; Candida albicans; Cell Wall; Child; Child, Preschool; Female; Humans; Immunoglobulins, Intravenous; Male; Mucocutaneous Lymph Node Syndrome; Prognosis

Intraperitoneal administration of CAWS (water-soluble extracellular polysaccharide fraction obtained from the culture supernatant of Candida albicans) to mice induces coronary arteritis similar to Kawasaki disease. We analyzed differences in the production of cytokines involved in the occurrence of coronary arteritis among mouse strains, C3H/HeN, C57BL/6, DBA/2 and CBA/J. The incidence of arteritis was 100% in C57BL/6, C3H/HeN and DBA/2 mice, but only 10% in CBA/J mice. The coronary arteritis observed in DBA/2 mice was the most serious, with several mice expiring during the observation period. The CAWS-sensitive strains revealed increased levels of IL-6 and IFN-gamma during the course of a specific response to CAWS by spleen cells. In contrast, IL-10 levels were observed to increase markedly in CAWS-resistant CBA/J mice, but not the CAWS-sensitive strains. However, TNF-alpha levels were more elevated only in DBA/2 mice. The difference in disease development and cytokine production strongly suggests that the genetic background of the immune response to CAWS contributes to the occurrence of coronary arteritis.

Topics: Animals; beta-Glucans; Candida albicans; Disease Models, Animal; Fungal Proteins; Membrane Glycoproteins; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Mucocutaneous Lymph Node Syndrome