Hygiene Hypothesis as the Etiology of Kawasaki Disease: Dysregulation of Early B Cell Development

Kawasaki disease (KD) is an acute systemic vasculitis that occurs predominantly in children under 5 years of age. Despite much study, the etiology of KD remains unknown. However, epidemiological and immunological data support the hygiene hypothesis as a possible etiology. It is thought that more ste...

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Main Author: Jong-Keuk Lee
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/22/12334
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author Jong-Keuk Lee
author_facet Jong-Keuk Lee
author_sort Jong-Keuk Lee
collection DOAJ
description Kawasaki disease (KD) is an acute systemic vasculitis that occurs predominantly in children under 5 years of age. Despite much study, the etiology of KD remains unknown. However, epidemiological and immunological data support the hygiene hypothesis as a possible etiology. It is thought that more sterile or clean modern living environments due to increased use of sanitizing agents, antibiotics, and formula feeding result in a lack of immunological challenges, leading to defective or dysregulated B cell development, accompanied by low IgG and high IgE levels. A lack of B cell immunity may increase sensitivity to unknown environmental triggers that are nonpathogenic in healthy individuals. Genetic studies of KD show that all of the KD susceptibility genes identified by genome-wide association studies are involved in B cell development and function, particularly in early B cell development (from the pro-B to pre-B cell stage). The fact that intravenous immunoglobulin is an effective therapy for KD supports this hypothesis. In this review, I discuss clinical, epidemiological, immunological, and genetic studies showing that the etiopathogenesis of KD in infants and toddlers can be explained by the hygiene hypothesis, and particularly by defects or dysregulation during early B cell development.
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spelling doaj.art-ab799210005d4cc98a99db55301fb03a2023-11-22T23:40:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122221233410.3390/ijms222212334Hygiene Hypothesis as the Etiology of Kawasaki Disease: Dysregulation of Early B Cell DevelopmentJong-Keuk Lee0Asan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 05505, KoreaKawasaki disease (KD) is an acute systemic vasculitis that occurs predominantly in children under 5 years of age. Despite much study, the etiology of KD remains unknown. However, epidemiological and immunological data support the hygiene hypothesis as a possible etiology. It is thought that more sterile or clean modern living environments due to increased use of sanitizing agents, antibiotics, and formula feeding result in a lack of immunological challenges, leading to defective or dysregulated B cell development, accompanied by low IgG and high IgE levels. A lack of B cell immunity may increase sensitivity to unknown environmental triggers that are nonpathogenic in healthy individuals. Genetic studies of KD show that all of the KD susceptibility genes identified by genome-wide association studies are involved in B cell development and function, particularly in early B cell development (from the pro-B to pre-B cell stage). The fact that intravenous immunoglobulin is an effective therapy for KD supports this hypothesis. In this review, I discuss clinical, epidemiological, immunological, and genetic studies showing that the etiopathogenesis of KD in infants and toddlers can be explained by the hygiene hypothesis, and particularly by defects or dysregulation during early B cell development.https://www.mdpi.com/1422-0067/22/22/12334Kawasaki diseasehygiene hypothesisB cellsintravenous immunoglobulin
spellingShingle Jong-Keuk Lee
Hygiene Hypothesis as the Etiology of Kawasaki Disease: Dysregulation of Early B Cell Development
International Journal of Molecular Sciences
Kawasaki disease
hygiene hypothesis
B cells
intravenous immunoglobulin
title Hygiene Hypothesis as the Etiology of Kawasaki Disease: Dysregulation of Early B Cell Development
title_full Hygiene Hypothesis as the Etiology of Kawasaki Disease: Dysregulation of Early B Cell Development
title_fullStr Hygiene Hypothesis as the Etiology of Kawasaki Disease: Dysregulation of Early B Cell Development
title_full_unstemmed Hygiene Hypothesis as the Etiology of Kawasaki Disease: Dysregulation of Early B Cell Development
title_short Hygiene Hypothesis as the Etiology of Kawasaki Disease: Dysregulation of Early B Cell Development
title_sort hygiene hypothesis as the etiology of kawasaki disease dysregulation of early b cell development
topic Kawasaki disease
hygiene hypothesis
B cells
intravenous immunoglobulin
url https://www.mdpi.com/1422-0067/22/22/12334
work_keys_str_mv AT jongkeuklee hygienehypothesisastheetiologyofkawasakidiseasedysregulationofearlybcelldevelopment