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Background:
Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs, with atypical clinical manifestations and indefinite diagnosis and treatment. So far, the etiology of the disease is not completely clear. Current studies have known the interaction of genetic system, endocrine system, infection, environment, and oth...
Citations
... MX2 activates the NOD-like receptor signaling pathway, promotes neutrophil in ltration, and may worsen the condition of SLE [14]. Another study identi ed 28 hub genes, such as RPS7, RPL19, RPS17, and RPS19, playing important roles in the occurrence, development, and prognosis of SLE [15]. Lv Juan et al. found common expression interactions among SLE-associated gene CD40LG extracted from CTD and seven differentially expressed long non-coding RNAs (HCG27, LINC02555, LINC02210, DHRS4-AS1, MIR600HG, DANCR, and LINC01278). ...
... In addition, results from immune cell in ltration showed a signi cantly higher proportion of central memory CD8 + T cells in SLE patients, which correlated positively with the selected biomarkers [18].In order to identify new biomarkers as diagnostic markers or therapeutic targets for systemic lupus erythematosus (SLE) and achieve personalized and differentiated precision medicine, this study employed bioinformatics analysis methods. We downloaded gene expression pro ling data of whole blood samples from SLE patients and healthy controls from the GEO database, and used the limma package to identify differentially expressed genes between SLE and normal population [15].In order to identify key genes and pathways in the pathogenesis of SLE, we performed WGCNA analysis and identi ed 14 co-expression modules. Among them, we selected the magenta module that was most relevant to SLE and identi ed it as the most important module associated with SLE. ...
Background：Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unclear mechanisms, limiting treatment options. Our study identifies potential core genes of SLE and their clinical applicability.
Method：Using differential expression and weighted gene co-expression network analysis (WGCNA), we identified novel susceptibility modules and associated core genes. Examination of these genes through KEGG and GO analyses revealed their roles. Diagnostic performance of the core genes was evaluated using column line plot models and Receiver Operating Characteristic (ROC) curves. We also assessed the correlation between core genes and immune infiltration and used Mendelian randomization to determine the causal effect of GYPB on SLE.
Results：The gene co-expression network constructed through WGCNA identified 144 key genes associated with SLE. The column line graph model demonstrated strong predictive power for SLE risk, with its diagnostic effectiveness validated by the ROC curve. A causal relationship was established between the top five core genes and immune cell infiltration in SLE. A negative correlation was observed between the gene GYPB and SLE, suggesting that GYPB might serve as a potential therapeutic target.
Conclusion：This investigation provides new insights into SLE molecular mechanisms and potential therapeutic avenues.
... This article has been retracted by Hindawi, as publisher, following an investigation undertaken by the publisher [1]. This investigation has uncovered evidence of systematic manipulation of the publication and peer-review process. ...
... (2,9,10,15,17) Esta patología se presenta mayoritariamente en mujeres teniendo un rango de relación de 8:1 a 15:1 si se compara con el sexo masculino; se ha observado asociación a genes de cromosomas sexuales, hormonas sexuales, la estabilidad de la microbiota intestinal, etc, pues la mayor prevalencia se ha determinado en las etapas de pre-pubertad y posmenopausia; (2) al ser más evidente durante la edad reproductiva comprende un reto médico y psicológico a la hora de tratar un embarazo o en su defecto planificación familiar; una de las características que resulta en una mayor posibilidad de presentar esta patología es, la etnia, puesto que se ha denotado un incremento en la severidad y prevalencia en mujeres afrodescendientes, asiáticas e hispanas en una relación 4:2 si se compara con aquellas mujeres blancas. (3,15,18,19) Sin embargo, Nusbaum J et al. (3) mencionan en su trabajo de revisión que a pesar de que el grupo de hombres que llegasen a ser afectados por LES es menor, en términos de agresividad de la enfermedad, presenta mayor progresión en cuanto a daño orgánico y como consecuencia, este sexo tendría peor pronóstico, mientras que Kim J-W et al. (2) añaden que por la aparición infrecuente en hombres, un diagnóstico y tratamiento retardados serían parcialmente responsables de un cuadro clínico agresivo; por otra parte, Hu H y He C, (20) concluyen que los pacientes varones con LES tienen mayor susceptibilidad a infecciones que las mujeres, incluyendo al nuevo coronavirus COVID-19, ya que la testosterona tiene un efecto inmunosupresor. ...
... (14) El tratamiento indicado se basa en el uso de glucocorticoides, así como inmunosupresores, aunque se considera que lo prolongado que resulta el uso de estos medicamentos condiciona un mayor daño hacia los órganos, puesto que se evidencia que el uso de altas dosis de glucocorticoides, ciclofosfamida e inmunosupresores dan paso a que el paciente con LES se mantenga susceptible a presentar infecciones. (14,20,22) ...
Introduction: Systemic Lupus Erythematosus is an autoimmune disease with a very heterogeneous clinical presentation mediated by both environmental and genetic factors, it is predominantly female with a 9:1 ratio compared to males, as well as by Afro-descendant ethnic groups, Asian and Hispanic; its pathogenesis is mediated by polymorphic variants of different genes that provide susceptibility to this disease and that have been related to different clinical characteristics, among the most notable are lupus nephritis, cardiovascular diseases, while its treatment is not established. Objective: to determine the genetic polymorphisms predisposing to the development of Systemic Lupus Erythematosus. Methodology: the PubMed search engine was used together with Boolean operators and descriptors in the English language. Based on the search results, the articles to be included in the review were determined by selection according to involvement in the subject. Results: sixteen genetic polymorphisms involved in the pathogenesis of systemic lupus erythematosus were found. Conclusion: polymorphisms explain the predisposition for the female sex, as well as the development of more severe clinical manifestations, highlighting lupus nephritis in specific ethnic groups such as Afro-descendants.
Background：Systemic lupus erythematosus is a chronic autoimmune disease characterized by systemic inflammation. The underlying mechanisms of the disease are not yet clear, resulting in limited treatment options. The aim of this study is to investigate the potential core genes of systemic lupus erythematosus and evaluate their clinical applications in predicting the disease.
Method：We employed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to explore novel susceptibility modules and core genes associated with systemic lupus erythematosus. Further investigation of these core genes was carried out using KEGG and GO analyses to examine their potential roles. We established column line plot models and ROC curves to evaluate the diagnostic performance of the core genes. Additionally, we investigated the correlation between the core genes and immune infiltration. Finally, based on genome-wide association studies, we conducted a Mendelian randomization study to determine the causal effect of GYPB on systemic lupus erythematosus.
Results：We used the WGCNA method to construct a gene co-expression network and identified the most relevant modules related to systemic lupus erythematosus (SLE), as well as 144 overlapping key genes. GO and KEGG pathway enrichment analysis revealed that these core genes are closely associated with pathways such as DNA polymerase complex, astral microtubule and transferase complex, Malaria, and Porphyrin metabolism. Through analysis using Cytoscape software, we found that the top 10 upregulated genes with high scores were SLC4A1, EPB42, FECH, GYPB, ALAS2, AHSP, GATA1, KLF1, SNCA, and DMTN. Additionally, we observed that the column line graph model performed well in predicting the risk of systemic lupus erythematosus, and the ROC curve indicated its effectiveness for diagnosis.
In the end, we confirmed a causal relationship between the top five ranked core genes and immune cell infiltration in systemic lupus erythematosus. Additionally, in the inverse-variance weighted analysis, we found a negative correlation between GYPB and systemic lupus erythematosus, with an odds ratio (OR) of 0.620 (95% confidence interval = 0.4056-0.948, p=0.02).
Conclusion：We used WGCNA to construct a gene co-expression network and identified the core genes associated with systemic lupus erythematosus. These core genes help uncover the molecular mechanisms of systemic lupus erythematosus and enable further investigation into potential therapeutic targets.
Pulmonary fibrosis, a serious complication of systemic lupus erythematosus (SLE) and coronavirus disease 2019 (COVID-19), leads to irreversible lung damage. However, the underlying mechanism of this condition remains unclear. In this study, we revealed the landscape of transcriptional changes in lung biopsies from individuals with SLE, COVID-19-induced pulmonary fibrosis, and idiopathic pulmonary fibrosis (IPF) using histopathology and RNA sequencing, respectively. Despite the diverse etiologies of these diseases, lung expression of matrix metalloproteinase genes in these diseases showed similar patterns. Particularly, the differentially expressed genes were significantly enriched in the pathway of neutrophil extracellular trap formation, showing similar enrichment signature between SLE and COVID-19. The abundance of Neutrophil extracellular traps (NETs) was much higher in the lungs of individuals with SLE and COVID-19 compared to those with IPF. In-depth transcriptome analyses revealed that NETs formation pathway promotes epithelial-mesenchymal transition (EMT). Furthermore, stimulation with NETs significantly up-regulated α-SMA, Twist, Snail protein expression, while decreasing the expression of E-cadherin protein in vitro. This indicates that NETosis promotes EMT in lung epithelial cells. Given drugs that are efficacious in degrading damaged NETs or inhibiting NETs production, we identified a few drug targets that were aberrantly expressed in both SLE and COVID-19. Among these targets, the JAK2 inhibitor Tofacitinib could effectively disrupted the process of NETs and reversed NET-induced EMT in lung epithelial cells. These findings support that the NETs/EMT axis, activated by SLE and COVID-19, contributes to the progression of pulmonary fibrosis. Our study also highlights that JAK2 as a potential target for the treatment of fibrosis in these diseases.
