Macrophages and cytotoxic T cells infiltrate the destructed mitral tissue in Kawasaki disease

Sugitani, Yuichiro; Furuno, Kenji; Sueishi, Katsuo; Hara, Toshiro

doi:10.1136/bcr-2017-223584

Cited by 9 publications

(9 citation statements)

References 15 publications

(6 reference statements)

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“…Several cell types, such as neutrophils, T cells, monocytes and macrophages, are derived from hematopoietic cells and are associated with the pathogenesis of KD. The results of immune infiltration analysis of changes in macrophages and monocytes using xCell were consistent with those reported by Sugitani et al (48) and Koizumi et al (49), who confirmed that macrophages and monocytes were upregulated in the acute phase of KD and downregulated following treatment. Similar to macrophages and monocytes, the changing trend in platelets was also consistent with previous studies and the degree of platelet increase was associated with the level of immunoglobulin (50).…”

Section: Discussionsupporting

confidence: 90%

Bioinformatics identification of hub genes and signaling pathways regulated by intravenous immunoglobulin treatment in acute Kawasaki disease

Huang

Ding

et al. 2021

Exp Ther Med

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Kawasaki disease (KD) is an acute, self-limiting form of vasculitis commonly encountered in infants and young children. Intravenous immunoglobulin (IVIG) is the primary drug used for the treatment of KD, which may significantly reduce the occurrence of coronary artery lesions. However, the specific molecular profile changes of KD caused by IVIG treatment have remained elusive and require further research. The present study was designed to identify key genes, pathways and immune cells affected by IVIG treatment using multiple bioinformatics analysis methods. The results suggested that myeloid cells and neutrophils were affected by IVIG treatment. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified that hematopoietic cell lineages and osteoclast differentiation may have an important role in the mechanism of action of IVIG treatment. Immune cell analysis indicated that the levels of monocytes, M1 macrophages, neutrophils and platelets were markedly changed in patients with KD after vs. prior to IVIG treatment. The key upregulated genes, including ZW10 interacting kinetochore protein, GINS complex subunit 1 and microRNA-30b-3p in whole blood cells of patients with KD following treatment with IVIG indicated that these IVIG-targeted molecules may have important roles in KD. In addition, these genes were further examined by literature review and indicated to be involved in cell proliferation, apoptosis and virus-related immune response in patients with KD. Therefore, the present results may provide novel insight into the mechanisms of action of IVIG treatment for KD.

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Section: Discussionsupporting

confidence: 90%

Bioinformatics identification of hub genes and signaling pathways regulated by intravenous immunoglobulin treatment in acute Kawasaki disease

Huang

Ding

et al. 2021

Exp Ther Med

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“…Thus, endocardial dysfunction serves as the most prevalent type of NCA in acute KD. Sugitani et al 22 encountered a 6‐month‐old male infant who suffered from a serve MR (Sellers classification III) after diagnosis of KD; the histopathological findings of mitral tissue showed that mononuclear inflammatory cells were scattered throughout the valve and immunohistochemically positive mainly for CD8 and CD68. In addition, myocarditis occurs also frequently in acute KD before CAA and mainly results from interstitial oedema and inflammation rather than myocardial cell necrosis 23,24 …”

Section: Discussionmentioning

confidence: 99%

Clinical observation of noncoronary cardiac abnormalities in Chinese children with Kawasaki disease

Liu

Qiu

et al. 2020

Eur J Clin Investigation

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Background Kawasaki disease (KD) is an acute, self‐limited vasculitis. Coronary artery aneurysm (CAA) serves as a major contributor to the long‐term prognosis of KD. In addition, acute KD usually also leads to several kinds of noncoronary cardiac abnormalities (NCA) involving the pericardium, myocardium and endocardium. Materials and methods A total of 142 Chinese children with KD were recruited from July 2015 to April 2018. Blood samples were collected at 24 hours pre‐intravenous immunoglobulin (IVIG) therapy. Several inflammatory mediators and biomarkers for acute myocardial infarction were detected. Echocardiography and electrocardiography (ECG) were performed. Results Plasma white blood cell counts (WBC) were significantly increased in patients with IVIG‐nonresponsive KD when compared with their IVIG‐responsive counterparts. A total of 106 children (74.65%) suffered from NCA, including 8 patients (5.63%) with pericardial effusion, 23 patients (16.20%) with acute myocarditis, 101 patients (71.13%) with valvular regurgitation and 8 patients (5.63%) with abnormal ECG. No significant differences were observed in the distribution of clinical classification and the response to IVIG therapy regardless of NCA exhibited or not. Conclusions Noncoronary cardiac abnormalities is almost universal in acute KD and mainly manifests as valvular regurgitation. However, it has no influence on clinical classification and the response to IVIG therapy.

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“…During the course of acute-stage KD, the inflammatory cells in coronary arteries consist mainly of infiltrating neutrophils and monocyte/macrophages, and these cells are involved in vascular damage [16,17]. Conversely, the inflammatory cells in lymph nodes consist mainly of lymphocytes, plasma cells, and monocytes/macrophages but include a relatively low number of neutrophils [18,19]. The relationship between immune cells such as neutrophils and monocyte/macrophage and predominant sites such as intravascular, perivascular, and extravascular lesions is not well known.…”

Section: Discussionmentioning

confidence: 99%

The Risk Prediction of Coronary Artery Lesions through the Novel Hematological Z-Values in 4 Chronological Age Subgroups of Kawasaki Disease

et al. 2020

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Background and Objectives: Most cases of Kawasaki disease (KD) occur between the ages of 6 months and 5 years. Differences in immunological reaction and CAL (coronary artery lesion) by the age subgroups classified according to the prevalence of KD and those particularly in the earlier life of KD should be investigated. Materials and Methods: The laboratory data of 223 infantile and 681 non-infantile KD cases from 2003 to 2018 at Korea University Hospital were retrospectively analyzed. Patients with KD were divided into infants and non-infants and further subdivided into four subgroups by age. The age-adjusted Z-values were compared among the subgroups. Febrile controls were identified as patients with fever for >5 days and who showed some of the KD symptoms. Results: IVIG (intravenous immunoglobulin) resistance at the age of 6 months or less was significantly lower than that at the ages of 7–12 months and 13–60 months (respectively, p < 0.05). The significant risk factors for CAL in total KD patients were age, incomplete KD, post-IVIG fever, IVIG resistance, convalescent Z-eosinophil, and subacute platelet (p < 0.05). The significant risk factors for CAL at the age of 6 months or less were IVIG resistance, acute Z-neutrophil, subacute Z-neutrophil, subacute NLR (neutrophil to lymphocyte ratio), and subacute platelet (respectively, p < 0.05). Conclusion: Younger age and incomplete presentation in KD can be independent risk factors for CAL. The immune reactions of KD at a younger age are more tolerated compared with those at older ages during the acute phase. The immune response at the age of 6 months or less showed immune tolerance in terms of incomplete presentation and IVIG responsiveness. The risk factors such as IVIG resistance, subacute platelet, subacute NLR, and acute or subacute Z-neutrophil at the age of 6 months or less can be very useful parameters to predict CAL in young, incomplete KD.

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Macrophages and cytotoxic T cells infiltrate the destructed mitral tissue in Kawasaki disease

Cited by 9 publications

References 15 publications

Bioinformatics identification of hub genes and signaling pathways regulated by intravenous immunoglobulin treatment in acute Kawasaki disease

Bioinformatics identification of hub genes and signaling pathways regulated by intravenous immunoglobulin treatment in acute Kawasaki disease

Clinical observation of noncoronary cardiac abnormalities in Chinese children with Kawasaki disease

The Risk Prediction of Coronary Artery Lesions through the Novel Hematological Z-Values in 4 Chronological Age Subgroups of Kawasaki Disease

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