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Differential alternative splicing events. (a) Summary of the differential alternative splicing event analysis results. (b) Read distribution plot of cell division cycle 6 (CDC6) with differential isoform expressions due to mutual exclusive exon (MXE). The histograms represent the abundance of the reads (blue represents CTRL1, red represents SLE19). Reads track, which directly displays the comparison of reads, is shown below the histograms. The green boxes represent the 1st exon or the 2nd exon where MXE occurs. (c) Sashimi plot is taken from the IGV Viewer that shows an MXE of the gene CDC6 that occurred in CTRL1 and SLE19. All of the splice junctions detected were labeled, and the numbers on the arc represent the read depths of the junctions.
Source publication
The multi-system involvement and high heterogeneity of systemic lupus erythematosus (SLE) pose great challenges to its diagnosis and treatment. The purpose of the current study is to identify genes and pathways involved in the pathogenesis of SLE. High throughput sequencing was performed on the PBMCs from SLE patients. We conducted differential gen...
Citations
... Additionally, we identified a downregulation of a core signature associated with cell cycle function in patients under remission compared to active patients. This finding aligns with previous research showing enrichment of disease-activity genes in cell cycle pathways, supporting the notion that dysregulated cell cycle processes contribute to SLE pathogenesis [43,44]. Although the expression levels of the genes in cell cycle module in remission patients were lower than in the active state, they remained higher than in healthy individuals. ...
Objectives
This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission.
Methods
We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks.
Results
Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse.
Conclusion
Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.
... Sequencing data analysis were performed as previously described by Yang et al. (17). Briefly, Raw sequencing data in fastq format were initially processed using in-house perl scripts. ...
Introduction
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). This study aimed to identify LN specific-genes and potential therapeutic targets.
Methods
We performed high-throughput transcriptome sequencing on peripheral blood mononuclear cells (PBMCs) from LN patients. Healthy individuals and SLE patients without LN were used as controls. To validate the sequencing results, qRT-PCR was performed for 5 upregulated and 5 downregulated genes. Furthermore, the effect of the TNFRSF17-targeting drug IBI379 on patient plasma cells and B cells was evaluated by flow cytometry.
Results
Our analysis identified 1493 and 205 differential genes in the LN group compared to the control and SLE without LN groups respectively, with 70 genes common to both sets, marking them as LN-specific. These LN-specific genes were significantly enriched in the ‘regulation of biological quality’ GO term and the cell cycle pathway. Notably, several genes including TNFRSF17 were significantly overexpressed in the kidneys of both LN patients and NZB/W mice. TNFRSF17 levels correlated positively with urinary protein levels, and negatively with complement C3 and C4 levels in LN patients. The TNFRSF17-targeting drug IBI379 effectively induced apoptosis in patient plasma cells without significantly affecting B cells.
Discussion
Our findings suggest that TNFRSF17 could serve as a potential therapeutic target for LN. Moreover, IBI379 is presented as a promising treatment option for LN.
... The database GSE211979 contains the transcriptome sequencing results of peripheral blood samples from 5 control subjects and 16 COVID-19 patients within 72 h after diagnosis [22]. The SLE patient databases used in this study include GSE112087 and GSE211700, which contain the transcriptome test results of peripheral blood samples from 31 SLE patients and 21 healthy controls and 10 healthy people and 20 SLE patients respectively [23,24]. ...
Background
The Coronavirus disease 2019 (COVID-19) pandemic has brought a heavy burden to the world, interestingly, it shares many clinical symptoms with systemic lupus erythematosus (SLE). It is unclear whether there is a similar pathological process between COVID-9 and SLE. In addition, we don’t know how to treat SLE patients with COVID-19. In this study, we analyse the potential similar pathogenesis between SLE and COVID-19 and explore their possible drug regimens using bioinformatics and systems biology approaches.
Methods
The common differentially expressed genes (DEGs) were extracted from the COVID-19 datasets and the SLE datasets for functional enrichment, pathway analysis and candidate drug analysis.
Result
Based on the two transcriptome datasets between COVID-19 and SLE, 325 common DEGs were selected. Hub genes were identified by protein-protein interaction (PPI) analysis. few found a variety of similar functional changes between COVID-19 and SLE, which may be related to the pathogenesis of COVID-19. Besides, we explored the related regulatory networks. Then, through drug target matching, we found many candidate drugs for patients with COVID-19 only or COVID-19 combined with SLE.
Conclusion
COVID-19 and SLE patients share many common hub genes, related pathways and regulatory networks. Based on these common targets, we found many potential drugs that could be used in treating patient with COVID-19 or COVID-19 combined with SLE.
... In RCDII-derived cell lines, treatment with PI3K inhibitor LY294002 also strongly inhibited proliferation triggered by IL-15 [58]. One of the mechanisms by which JAK/STAT and PI3K/AKT pathways promote proliferation during IL-15 signalling is through the upregulation of telomerase which maintains telomere length for continuous proliferation in NK, NKT, and T MEM [89][90][91][92]. ...
There is an intriguing dichotomy in the function of cytokine Interleukin-15 – at low levels, it is required for the homeostasis of the immune system, yet when it is upregulated in response to pathogenic infections or in autoimmunity, IL-15 drives inflammation. IL-15 associates with the IL-15Rα within both myeloid and non-haematopoietic cells, where IL-15Rα trans-presents IL-15 in a membrane-bound form to neighbouring cells. Alongside homeostatic maintenance of select lymphocyte populations such as NK cells and tissue-resident T cells, when upregulated, IL-15 also promotes inflammatory outcomes by driving effector function and cytotoxicity in NK cells and T cells. As chronic overexpression of IL-15 drives autoimmunity, IL-15 expression is tightly regulated. Thus, blocking dysregulated IL-15 and its downstream signalling pathways are avenues for immunotherapy. In this review we discuss the molecular pathways involved in IL-15 signalling and how these pathways contribute to both homeostatic and inflammatory functions in IL-15-dependent mature lymphoid populations, focusing on innate and innate-like lymphocytes in tissues.
