Altered Monocyte Subsets in Kawasaki Disease Revealed by Single-cell RNA-Sequencing

Geng, Zhimin; Tao, Yijing; Zheng, Fei; Wu, Linlin; Wang, Ying; Wang, Yujia; Sun, Yameng; Fu, Songling; Wang, Wei; Xie, Chunhong; Zhang, Yiying; Gong, Fangqi

doi:10.2147/jir.s293993

Cited by 28 publications

(32 citation statements)

References 44 publications

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“…Although the etiology of KD remains unknown, several studies have shown that it might develop as a consequence of an aberrant immune response ( 114 ). This was confirmed by two different studies performing scRNA-seq in PBMCs of KD patients ( 108 , 109 ) ( Table 4 ). The first one identified 14 cell clusters in KD samples, with expanded populations of natural killer T (NKT) cells and pDC, and lower frequency of naïve CD8 + T cells, T helper cells, B cells, and lymphoid progenitor cells.…”

Section: Application Of Scrna-seq In Autoimmune Inflammatory Rheumatic Diseasessupporting

confidence: 61%

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Single Cell RNA Sequencing in Autoimmune Inflammatory Rheumatic Diseases: Current Applications, Challenges and a Step Toward Precision Medicine

et al. 2022

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Single cell RNA sequencing (scRNA-seq) represents a new large scale and high throughput technique allowing analysis of the whole transcriptome at the resolution of an individual cell. It has emerged as an imperative method in life science research, uncovering complex cellular networks and providing indices that will eventually lead to the development of more targeted and personalized therapies. The importance of scRNA-seq has been particularly highlighted through the analysis of complex biological systems, in which cellular heterogeneity is a key aspect, such as the immune system. Autoimmune inflammatory rheumatic diseases represent a group of disorders, associated with a dysregulated immune system and high patient heterogeneity in both pathophysiological and clinical aspects. This complicates the complete understanding of underlying pathological mechanisms, associated with limited therapeutic options available and their long-term inefficiency and even toxicity. There is an unmet need to investigate, in depth, the cellular and molecular mechanisms driving the pathogenesis of rheumatic diseases and drug resistance, identify novel therapeutic targets, as well as make a step forward in using stratified and informed therapeutic decisions, which could now be achieved with the use of single cell approaches. This review summarizes the current use of scRNA-seq in studying different rheumatic diseases, based on recent findings from published in vitro, in vivo, and clinical studies, as well as discusses the potential implementation of scRNA-seq in the development of precision medicine in rheumatology.

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Section: Application Of Scrna-seq In Autoimmune Inflammatory Rheumatic Diseasessupporting

confidence: 61%

“…Classical monocytes in KD might thus have a less differentiated phenotype compared to their healthy counterparts. Altered monocyte subpopulations might be considered as biomarkers for KD diagnosis and treatment ( 109 ).…”

Section: Application Of Scrna-seq In Autoimmune Inflammatory Rheumatic Diseasesmentioning

confidence: 99%

Single Cell RNA Sequencing in Autoimmune Inflammatory Rheumatic Diseases: Current Applications, Challenges and a Step Toward Precision Medicine

et al. 2022

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“…Effects of the immune microenvironment on the pathogenesis of KD have been well-reported in many studies, and most of them underscore the importance of the innate immune system in the acute phase of KD. Particularly, levels of monocytes/macrophages and neutrophils were markedly upregulated in children with KD ( 25 , 30 , 31 ). Our results were also in agreement with these reports from high-throughput studies ( 30 , 31 ).…”

Section: Discussionmentioning

confidence: 99%

“…Particularly, levels of monocytes/macrophages and neutrophils were markedly upregulated in children with KD ( 25 , 30 , 31 ). Our results were also in agreement with these reports from high-throughput studies ( 30 , 31 ). In our diagnostic score, the proportion of macrophages and neutrophils weighed heavy.…”

Section: Discussionmentioning

confidence: 99%

A Diagnostic Model for Kawasaki Disease Based on Immune Cell Characterization From Blood Samples

Mansmann

Geisler

et al. 2022

Front. Pediatr.

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Background: Kawasaki disease (KD) is the leading cause of acquired heart disease in children. However, distinguishing KD from febrile infections early in the disease course remains difficult. Our goal was to estimate the immune cell composition in KD patients and febrile controls (FC), and to develop a tool for KD diagnosis.Methods: We used a machine-learning algorithm, CIBERSORT, to estimate the proportions of 22 immune cell types based on blood samples from children with KD and FC. Using these immune cell compositions, a diagnostic score for predicting KD was then constructed based on LASSO regression for binary outcomes.Results: In the training set (n = 496), a model was fit which consisted of eight types of immune cells. The area under the curve (AUC) values for diagnosing KD in a held-out test set (n = 212) and an external validation set (n = 36) were 0.80 and 0.77, respectively. The most common cell types in KD blood samples were monocytes, neutrophils, CD4+-naïve and CD8+ T cells, and M0 macrophages. The diagnostic score was highly correlated to genes that had been previously reported as associated with KD, such as interleukins and chemokine receptors, and enriched in reported pathways, such as IL-6/JAK/STAT3 and TNFα signaling pathways.Conclusion: Altogether, the diagnostic score for predicting KD could potentially serve as a biomarker. Prospective studies could evaluate how incorporating the diagnostic score into a clinical algorithm would improve diagnostic accuracy further.

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“…Kawasaki disease (KD) is an acute, self-limiting disease that is characterized by systemic vasculitis and is the leading cause of acquired heart disease in children in developed countries [ 1 , 2 ]. KD occurs mainly in children who are younger than 5 years and is less common in older children [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Analysis Reveals the Role of the Neuropeptide Receptor FPR2 in Monocytes in Kawasaki Disease: A Bioinformatic Study

et al. 2022

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Exploring the role of neuropeptides in the communication between monocyte subtypes facilitates an investigation of the pathogenesis of Kawasaki disease (KD). We investigated the patterns of interaction between neuropeptide-associated ligands and receptors in monocyte subpopulations in KD patients. Single-cell analysis was employed for the identification of cell subpopulations in KD patients, and monocytes were classified into 3 subpopulations: classical monocytes (CMs), intermediate monocytes (IMs), and nonclassical monocytes (NCMs). Cell-cell communication and differential analyses were used to identify ligand-receptor interactions in monocytes. Five neuropeptide-related genes (SORL1, TNF, SORT1, FPR2, and ANXA1) were involved in cell-cell interactions, wherein FPR2, a neuropeptide receptor, was significantly highly expressed in KD. Weighted gene coexpression network analysis revealed a significant correlation between the yellow module and FPR2 ( p < 0.001 , CC = 0.43 ). Using the genes in the yellow module, we constructed a PPI network to assess the possible functions of the FPR2-associated gene network. Gene set enrichment analysis showed that increased FPR2 levels may be involved in immune system regulation. FPR2 in CMs mediates the control of inflammation in KD. The findings of this study may provide a novel target for the clinical treatment of KD.

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Altered Monocyte Subsets in Kawasaki Disease Revealed by Single-cell RNA-Sequencing

Cited by 28 publications

References 44 publications

Single Cell RNA Sequencing in Autoimmune Inflammatory Rheumatic Diseases: Current Applications, Challenges and a Step Toward Precision Medicine

Single Cell RNA Sequencing in Autoimmune Inflammatory Rheumatic Diseases: Current Applications, Challenges and a Step Toward Precision Medicine

A Diagnostic Model for Kawasaki Disease Based on Immune Cell Characterization From Blood Samples

Single-Cell Analysis Reveals the Role of the Neuropeptide Receptor FPR2 in Monocytes in Kawasaki Disease: A Bioinformatic Study

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