scholarly journals Crucial transcripts predict response to initial immunoglobulin treatment in acute Kawasaki disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhimin Geng ◽  
Jingjing Liu ◽  
Jian Hu ◽  
Ying Wang ◽  
Yijing Tao ◽  
...  

Abstract Although intravenous immunoglobulin (IVIG) can effectively treat Kawasaki disease (KD), 10–20% of KD patients show no beneficial clinical response. Developing reliable criteria to discriminate non-responders is important for early planning of appropriate regimens. To predict the non-responders before IVIG treatment, gene expression dataset of 110 responders and 61 non-responders was obtained from Gene Expression Omnibus. After weighted gene co-expression network analysis, we found that modules positively correlated with the non-responders were mainly associated with myeloid cell activation. Transcripts up-regulated in the non-responders, IL1R2, GK, HK3, C5orf32, CXCL16, NAMPT and EMILIN2, were proven to play key roles via interaction with other transcripts in co-expression network. The crucial transcripts may affect the clinical response to IVIG treatment in acute KD. And these transcripts may serve as biomarkers and therapeutic targets for precise diagnosis and treatment of the non-responders.

2013 ◽  
Vol 163 (2) ◽  
pp. 521-526.e1 ◽  
Author(s):  
Tohru Kobayashi ◽  
Tomio Kobayashi ◽  
Akihiro Morikawa ◽  
Kentaro Ikeda ◽  
Mitsuru Seki ◽  
...  

The Lancet ◽  
1989 ◽  
Vol 334 (8675) ◽  
pp. 1298-1302 ◽  
Author(s):  
DonaldY.M. Leung ◽  
Evelyn Kurt-Jones ◽  
JaneW. Newburger ◽  
RamziS. Cotran ◽  
JaneC. Burns ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrea R. Daamen ◽  
Prathyusha Bachali ◽  
Katherine A. Owen ◽  
Kathryn M. Kingsmore ◽  
Erika L. Hubbard ◽  
...  

AbstractSARS-CoV2 is a previously uncharacterized coronavirus and causative agent of the COVID-19 pandemic. The host response to SARS-CoV2 has not yet been fully delineated, hampering a precise approach to therapy. To address this, we carried out a comprehensive analysis of gene expression data from the blood, lung, and airway of COVID-19 patients. Our results indicate that COVID-19 pathogenesis is driven by populations of myeloid-lineage cells with highly inflammatory but distinct transcriptional signatures in each compartment. The relative absence of cytotoxic cells in the lung suggests a model in which delayed clearance of the virus may permit exaggerated myeloid cell activation that contributes to disease pathogenesis by the production of inflammatory mediators. The gene expression profiles also identify potential therapeutic targets that could be modified with available drugs. The data suggest that transcriptomic profiling can provide an understanding of the pathogenesis of COVID-19 in individual patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yang Zhao ◽  
Jiaoyun Lv ◽  
Hongwei Zhang ◽  
Jiawei Xie ◽  
Hui Dai ◽  
...  

BackgroundPigmented villonodular synovitis (PVNS) is a rare condition that involves benign proliferation of the synovial tissue and is characterized by severe joint destruction and high recurrence even after surgical resection. However, poor understanding of the pathogenesis limits its effective therapy.MethodIn this study, gene expression profiles of six patients with PVNS, 11 patients with osteoarthritis (OA), nine patients with rheumatoid arthritis (RA) (E-MTAB-6141), and three healthy subjects (GSE143514) were analyzed using integrating RNA sequencing (RNA-seq) and microarray to investigate the PVNS transcriptome. Gene ontology, string, and cytoscape were used to determine the gene functional enrichment. Cell functional molecules were detected using flow cytometry or immunohistochemical test to identify the cell subset and function. CD14+ cells were isolated and induced to osteoclast to evaluate the monocyte/macrophage function.ResultsThe most obvious local manifestations of PVNS were inflammation, including increased immune cells infiltration and cytokine secretion, and tumor phenotypes. High proportion of inflammatory cells, including T cells, natural killer (NK) cells, NKT cells, and B cells were recruited from the blood. Th17 and monocytes, especially classical monocytes but not nonclassical monocytes, increased in PVNS synovium. An obvious increase in osteoclastogenesis and macrophage activation was observed locally. Elevated expression of MMP9, SIGLEC 15, and RANK were observed in myeloid cell of PVNS than OA. When compared with RA, osteoclast differentiation and myeloid cell activation are PVNS-specific characters, whereas T cell activation is shared by PVNS and RA.ConclusionThe transcriptional expression characteristics of PVNS showed increased immune response, cell migration, and osteoclastogenesis. Osteoclast differentiation is only observed in PVNS but not RA, whereas T-cell activation is common in inflammatory arthritis.


Author(s):  
Andrea R. Daamen ◽  
Prathyusha Bachali ◽  
Katherine A. Owen ◽  
Kathryn M. Kingsmore ◽  
Erika L. Hubbard ◽  
...  

AbstractSARS-CoV2 is a previously uncharacterized coronavirus and causative agent of the COVID-19 pandemic. The host response to SARS-CoV2 has not yet been fully delineated, hampering a precise approach to therapy. To address this, we carried out a comprehensive analysis of gene expression data from the blood, lung, and airway of COVID-19 patients. Our results indicate that COVID-19 pathogenesis is driven by populations of myeloid-lineage cells with highly inflammatory but distinct transcriptional signatures in each compartment. The relative absence of cytotoxic cells in the lung suggests a model in which delayed clearance of the virus may permit exaggerated myeloid cell activation that contributes to disease pathogenesis by the production of inflammatory mediators. The gene expression profiles also identify potential therapeutic targets that could be modified with available drugs. The data suggest that transcriptomic profiling can provide an understanding of the pathogenesis of COVID-19 in individual patients.Graphical Abstract


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11169
Author(s):  
Changsheng Guo ◽  
Yuanqing Hua ◽  
Zuanhao Qian

Background Kawasaki disease (KD) is an acute and febrile systemic vasculitis of unknown etiology. This study aimed to identify the competing endogenous RNA (ceRNA) networks of lncRNAs, miRNAs, and genes in KD and explore the molecular mechanisms underlying KD. Methods GSE68004 and GSE73464 datasets were downloaded from the Gene Expression Omnibus. Differentially expressed lncRNAs (DElncRNAs) and genes (DEGs) in KD were identified using the criteria of p < 0.05 and | log2 (fold change) | ≥ 1. MicroRNAs (miRNAs) related to KD were searched from databases. The lncRNA-miRNA-mRNA networks involving the DElncRNAs and DEGs were constructed. Results A total of 769 common upregulated, 406 common downregulated DEGs, and six DElncRNAs were identified in the KD samples. The lncRNA-miRNA-mRNA network consisted of four miRNAs, three lncRNAs (including the upregulated PSORS1C3, LINC00999, and the downregulated SNHG5) and four DEGs (including the downregulated GATA3 and the upregulated SOD2, MAPK14, and PPARG). Validation in the GSE18606 dataset showed that intravenous immunoglobulin treatment significantly alleviated the deregulated profiles of the above RNAs in KD patients. Three ceRNA networks of LINC00999-hsa-miR-6780-SOD2, PSORS1C3-hsa-miR-216a-PPARG/MAPK14, and SNHG5-hsa-miR-132/hsa-miR-92-GATA3 were identified. Four genes were associated with functional categories, such as inflammatory response and vascular endothelial cell. Conclusions The ceRNA networks involve genes, such as SOD2, MAPK14, and PPARG, and lncRNAs, including PSORS1C3, LINC00999, and SNHG5, which might play a key role in the pathogenesis and development of KD by regulating inflammation.


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