Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota

Kaneko, Kazunari; Akagawa, Shohei; Akagawa, Yuko; Kimata, Takahisa

doi:10.3389/fimmu.2020.01616

Cited by 31 publications

(21 citation statements)

References 104 publications

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“…In KD, hyperinflammation is hypothesized to be due to an imbalance between T-helper 17 cells and regulatory T cells [ 49 ]. In MIS-C, SARS-CoV-2 is thought to be the trigger [ 39 ].…”

Section: Pathogenesismentioning

confidence: 99%

Multisystem Inflammatory Syndrome in Children Related to SARS-CoV-2

Esposito

Principi

2021

Pediatr Drugs

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Although data on the incidence and severity of new coronavirus disease 2019 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection showed more significant disease among adults and the elderly, a clinical manifestation characterized by a multisystem inflammatory syndrome was described in children (MIS-C). It was initially thought to be specific to children, but recent reports have shown that it can also occur in adults. MIS-C is characterized by a number of multisystemic manifestations resembling other known previously described illnesses, mainly Kawasaki disease, especially in cases with shock, toxic shock syndrome, and macrophage activation syndrome. Available literature shows that our knowledge of MIS-C is largely incomplete. Its development in strict relation with SARS-CoV-2 infection seems documented and, in most cases, can be considered a post-infectious manifestation secondary to an abnormal immune response for some aspects, similar to that seen in adults several days after SARS-CoV-2 infection. However, in a minority of cases, a clinical picture with symptoms fulfilling criteria for MIS-C diagnosis develops during the acute phase of SARS-CoV-2 infection. It is highly likely that the criteria currently used to diagnose MIS-C are too broad, meaning that children with different diseases are included. As clarity on the pathogenesis of MIS-C is lacking, different therapeutic approaches have been used, but no specific therapy is currently available. Further studies are urgently needed to improve our definition of MIS-C, to define the real impact on child health, and to elucidate the best clinical and therapeutic approach and true prognosis.

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“…In KD, hyperinflammation is hypothesized to be due to an imbalance between T-helper 17 cells and regulatory T cells [ 49 ]. In MIS-C, SARS-CoV-2 is thought to be the trigger [ 39 ].…”

Section: Pathogenesismentioning

confidence: 99%

Multisystem Inflammatory Syndrome in Children Related to SARS-CoV-2

Esposito

Principi

2021

Pediatr Drugs

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“…Despite extensive research, the underlying mechanisms of KD remain unknown [ 1 ]. The current paradigm on this enigmatic vasculitis pathogenesis is that the disease results from an exaggerated immune response towards infectious agent(s) in a genetically and environmentally susceptible child [ 9 , 10 ]. Genetically determined susceptibility includes polymorphisms in the genes encoding cytokines, chemokines, and enzymes involved in signal transduction.…”

Section: Discussionmentioning

confidence: 99%

Combined Single Nucleotide Variants of ORAI1 and BLK in a Child with Refractory Kawasaki Disease

et al. 2021

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Kawasaki disease (KD) is a systemic vasculitis with an unknown etiology affecting young children. Although intravenous immunoglobulin (IVIG) plus acetylsalicylic acid is effective in most cases, approximately 10–20% of patients do not respond to this therapy. An 8-month-old boy was admitted to a local hospital with the presumptive diagnosis of KD. He received IVIG twice and four series of methylprednisolone pulse therapy from the third to the tenth day of illness. Despite these treatments, his fever persisted with the development of moderate dilatations of the coronary arteries. A diagnosis of refractory KD was made, and infliximab with oral prednisolone was administered without success. Defervescence was finally achieved by cyclosporine A, an inhibitor of the signaling pathway of the calcineurin/nuclear factor of activated T cells (NFAT). Whole-genome sequencing of his deoxyribonucleic acid samples disclosed two single nucleotide variants (SNVs) in disease-susceptibility genes in Japanese KD patients, ORAI1 (rs3741596) and BLK (rs2254546). In summary, the refractory nature of the present case could be explained by the presence of combined SNVs in susceptibility genes associated with upregulation of the calcineurin/NFAT signaling pathway. It may provide insights for stratifying KD patients based on the SNVs in their susceptibility genes.

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“…Dysbiosis is associated with increased risk of gastrointestinal diseases, such as inflammatory intestinal disorder [ 11 , 12 ], irritable bowel syndrome [ 13 ], and necrotizing enterocolitis [ 14 ]; allergic diseases [ 15 , 16 ]; diabetes [ 17 ]; obesity [ 18 , 19 ]; cardiovascular disease [ 20 ]; autism spectrum disorder [ 21 ]; and sudden infant death syndrome [ 22 ]. We propose that dysbiosis may also be present in children with idiopathic nephrotic syndrome [ 23 , 24 , 25 ] and Kawasaki disease [ 26 ].…”

Section: Development Of the Gut Microbiota And Diseasesmentioning

confidence: 99%

Development of the gut microbiota and dysbiosis in children

Akagawa

Yamanouchi

et al. 2021

Bioscience of Microbiota, Food and Health

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The gut microbiota resides in the human gastrointestinal tract, where it plays an important role in maintaining host health. Recent advancements in next-generation sequencing methods have revealed the link between dysbiosis (imbalance of the normal gut microbiota) and several diseases, as this imbalance can disrupt the symbiotic relationship between the host and associated microbes. Establishment of the gut microbiota starts in utero or just after birth, and its composition dramatically changes to an adult-like composition by 3 years of age. Because dysbiosis during childhood may persist through adulthood, it is crucial to acquire a balanced gut microbiota in childhood. Therefore, current studies have focused on the factors affecting the infant gut microbiota. This review discusses recent findings, including those from our studies, on how various factors, including the delivery mode, feeding type, and administration of drugs, including antibiotics, can influence the infant gut microbiota. Here, we also address future approaches for the prevention and restoration of dysbiosis in children.

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Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota

Cited by 31 publications

References 104 publications

Multisystem Inflammatory Syndrome in Children Related to SARS-CoV-2

Multisystem Inflammatory Syndrome in Children Related to SARS-CoV-2

Combined Single Nucleotide Variants of ORAI1 and BLK in a Child with Refractory Kawasaki Disease

Development of the gut microbiota and dysbiosis in children

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