A framework for understanding Kawasaki disease pathogenesis

Lo, Mindy S.

doi:10.1016/j.clim.2020.108385

Cited by 45 publications

(33 citation statements)

References 87 publications

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“…In this study, we found that serum sSema4D was significantly increased in KD patients compared with healthy controls, which is similar to the investigations of sSema4D in coronary heart disease [ 13 ] and autoimmune diseases [ 11 ]. KD is characterized by cardiovascular complications and the autoimmune process [ 26 , 27 ], and both phenotypes are implicated in the inflammatory response. Thus, we deduced that elevation of circulating sSema4D may be a common phenomenon in inflammatory conditions, including KD.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil‐Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease

Huang

Cao

et al. 2020

BioMed Research International

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Inflammation of endothelial cells (ECs) plays an important role in the pathogenesis of coronary artery lesions (CALs) in Kawasaki disease (KD). Semaphorin 4D (Sema4D) is the first semaphorin shown to have immunoregulatory functions by interacting with its receptors—plexin Bs. Recently, Sema4D has been reported to exert a proinflammatory effect on the endothelium and to be involved in cardiovascular disease. However, the role of Sema4D in KD remains unknown. This study was aimed at revealing the change of soluble Sema4D (sSema4D) in the serum of patients with KD and the effect of the sSema4D-plexin axis on the production of proinflammatory cytokines from human coronary endothelial cells (HCAECs) stimulated with sera from KD patients. Our results showed that serum sSema4D levels were specifically elevated in KD patients, especially in those with CALs, and correlated positively with disease severity and serum concentrations of interleukin- (IL-) 1β, IL-6, and IL-8. The disintegrin and metalloproteinase domain 17- (AMAM17-) mediated Sema4D shedding from neutrophils contributed to the elevation of sSema4D in the serum of KD patients. Furthermore, we found that Sema4D induced IL-1β production of HCAECs via plexin B2, whereas it promoted IL-6 and IL-8 production via plexin B1. Moreover, the expression of both plexin B1 and plexin B2 was upregulated in HCAECs treated with KD sera, and silencing of the two plexin receptors suppressed the overexpression of IL-1β, IL-6, and IL-8 in KD serum-treated HCAECs. Thus, our findings indicated that sSema4D released from neutrophils participates in the pathogenesis of KD-CALs by promoting inflammatory cytokine production of ECs via both plexin B1 and plexin B2, and Sema4D may be a novel predictor for KD-CALs and a candidate therapeutic target for anti-inflammatory strategies of KD.

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Section: Discussionmentioning

confidence: 99%

Neutrophil‐Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease

Huang

Cao

et al. 2020

BioMed Research International

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“…Various observations support this hypothesis: (i) KD prevalence is higher in East Asian populations, even in transmigration areas; (ii) African American children are disproportionately affected by KD as compared to Caucasian people 41 ; (iii) nearly all instances of children with COVID-19-associated KD-like symptoms have occurred in western countries in which individuals of African descent are largely prevalent. In addition, Lo 42 and Onouchi 43 have described potential KD genetic susceptibilities such as FCGR2A, BLK, CD40, ITPKC , and CASP3 from genome-wide association studies. Among the other factors implicated in the disease, Yoshida et al .…”

Section: Kawasaki-like Syndromementioning

confidence: 99%

“…Fine particles might associate with viral particles directly, or may indirectly improve cell entry in host airways by their chronic inflammation of epithelial cell walls. It should also be noted that KD pathogenesis appears to be associated with certain environmental factors, 42 as well as with a certain genetic background, and with infectious trigger pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). Besides seasonal factors, tropospheric wind patterns have also been linked to KD.…”

Section: Environmental Exposurementioning

confidence: 99%

Host/genetic factors associated with COVID-19 call for precision medicine

Thierry

2020

Precision Clinical Medicine

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If the current rates of infection are to be better managed, and future waves of infection kept at bay, it is absolutely necessary that the conditions and mechanisms of exposure to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) be better understood, as well as the downstream severe or lethal clinical complications. While the identification of notable comorbidities has now helped to define broad risk groups, the idiosyncratic responses of individual patients can nonetheless generate unexpected clinical deterioration which is difficult to predict from initial clinical features. Thus, physicians caring for COVID-19 patients face clinical dilemmas on a daily basis. The ability to decipher individual predispositions to SARS-CoV-2 infection or severe illness, in light of variations in host immunological and inflammatory responses, in particular due to genetic variations, would be of great benefit in infection management. To this end, this work associates the description of COVID-19 clinical complications, comorbidities, sequelae and environmental and genetic factors. We also give examples of underlying genomic susceptibility to COVID-19, especially with regard to the newly reported link between the disease and the unbalanced formation of neutrophil extracellular traps. As a consequence, we propose that the host/genetic factors associated with COVID-19 call for precision medicine in its treatment. This is to our knowledge the first article describing elements towards precision medicine for COVID-19 patients.

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“…Giordani et al (2) confirmed the hypothesis of an infectious triggered overexpression of inflammatory cytokines in KD. Many known and unknown infectious agents have been linked to KD, such as bacterial, viral, and fungal agents, and whether a single as-yet unidentified agent is responsible or whether multiple agents can produce a similar pattern of symptoms in genetically predisposed individuals was unknown (3).…”

Section: Introductionmentioning

confidence: 99%

Combined IFN-β and PLT Detection Can Identify Kawasaki Disease Efficiently

et al. 2021

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Objective: To evaluate the value of combined interferon β (IFN-β) and platelet (PLT) detection for Kawasaki disease (KD) identification.Methods: Forty-four children who were newly diagnosed with KD were selected as the KD group. They were divided into acute phase of KD and subacute phase of KD. They were also separated into groups with and without coronary artery disease (CAD) (CAD+ and CAD–, respectively). Meanwhile, 44 children hospitalized with febrile disease and 44 healthy children were selected as a febrile control group and normal control group, whom were attended to at Children's Hospital of Soochow University at the same time. We detected the concentration of IFN-β and PLT of peripheral blood serum for all three groups and analyzed the difference.Results: At acute and subacute phases of KD, both IFN-β and PLT are higher than both the febrile control group and healthy control group, especially at subacute phase; the difference between groups was statistically significant, P < 0.05. Receiver operating characteristic (ROC) curve showed that the areas under the ROC curve (AUCs) of IFN-β and PLT at acute phase of KD were 0.81 and 0.72, respectively; the sensitivity and specificity were 97.22 and 63.64%, and 57.89 and 73.86%, respectively. The AUCs of combined IFN-β and PLT were 0.81 at acute phase and 0.96 at subacute phase of KD, with sensitivity and specificity of 97.22 and 55.26%, and 86.36 and 100%, respectively. The cutoff value of combined IFN-β and PLT detection was IFN-β = 3.51 pg/ml and PLT = 303 × 109/L at acute phase of KD, IFN-β = 4.21 pg/ml and PLT = 368 × 109/L at subacute phase from plot vs. criterion values. However, there are no significant differences between the CAD– group and the CAD+ group for combined IFN-β and PLT, both P > 0.5, neither at acute nor at subacute phase of KD.Conclusion: Combined IFN-β and PLT detection is an efficient biomarker for KD identification. The cutoff values are IFN-β = 3.51 pg/ml and PLT = 303 × 109/L at acute phase of KD and IFN-β = 4.21 pg/ml and PLT = 368 × 109/L at subacute phase.

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A framework for understanding Kawasaki disease pathogenesis

Cited by 45 publications

References 87 publications

Neutrophil‐Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease

Neutrophil‐Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease

Host/genetic factors associated with COVID-19 call for precision medicine

Combined IFN-β and PLT Detection Can Identify Kawasaki Disease Efficiently

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