Pub Date : 2024-12-01Epub Date: 2024-03-22DOI: 10.1080/08916934.2024.2330392
Qiubai Jin, Feihong Ren, Ping Song
Background: Despite growing knowledge regarding the pathogenesis of autoimmune diseases (ADs) onset, the current treatment remains unsatisfactory. This study aimed to identify innovative therapeutic targets for ADs through various analytical approaches.
Research design and methods: Utilizing Mendelian randomization, Bayesian co-localization, phenotype scanning, and protein-protein interaction network, we explored potential therapeutic targets for 14 ADs and externally validated our preliminary findings.
Results: This study identified 12 circulating proteins as potential therapeutic targets for six ADs. Specifically, IL12B was judged to be a risk factor for ankylosing spondylitis (p = 1.61E - 07). TYMP (p = 6.28E - 06) was identified as a protective factor for ulcerative colitis. For Crohn's disease, ERAP2 (p = 4.47E - 14), HP (p = 2.08E - 05), and RSPO3 (p = 6.52E - 07), were identified as facilitators, whereas FLRT3 (p = 3.42E - 07) had a protective effect. In rheumatoid arthritis, SWAP70 (p = 3.26E - 10), SIGLEC6 (p = 2.47E - 05), ISG15 (p = 3.69E - 05), and FCRL3 (p = 1.10E - 10) were identified as risk factors. B4GALT1 (p = 6.59E - 05) was associated with a lower risk of Type 1 diabetes (T1D). Interestingly, CTSH was identified as a protective factor for narcolepsy (p = 1.58E - 09) but a risk factor for T1D (p = 7.36E - 11), respectively. External validation supported the associations of eight of these proteins with three ADs.
Conclusions: Our integrated study identified 12 potential therapeutic targets for ADs and provided novel insights into future drug development for ADs.
{"title":"Innovate therapeutic targets for autoimmune diseases: insights from proteome-wide mendelian randomization and Bayesian colocalization.","authors":"Qiubai Jin, Feihong Ren, Ping Song","doi":"10.1080/08916934.2024.2330392","DOIUrl":"10.1080/08916934.2024.2330392","url":null,"abstract":"<p><strong>Background: </strong>Despite growing knowledge regarding the pathogenesis of autoimmune diseases (ADs) onset, the current treatment remains unsatisfactory. This study aimed to identify innovative therapeutic targets for ADs through various analytical approaches.</p><p><strong>Research design and methods: </strong>Utilizing Mendelian randomization, Bayesian co-localization, phenotype scanning, and protein-protein interaction network, we explored potential therapeutic targets for 14 ADs and externally validated our preliminary findings.</p><p><strong>Results: </strong>This study identified 12 circulating proteins as potential therapeutic targets for six ADs. Specifically, IL12B was judged to be a risk factor for ankylosing spondylitis (<i>p</i> = 1.61E - 07). TYMP (<i>p</i> = 6.28E - 06) was identified as a protective factor for ulcerative colitis. For Crohn's disease, ERAP2 (<i>p</i> = 4.47E - 14), HP (<i>p</i> = 2.08E - 05), and RSPO3 (<i>p</i> = 6.52E - 07), were identified as facilitators, whereas FLRT3 (<i>p</i> = 3.42E - 07) had a protective effect. In rheumatoid arthritis, SWAP70 (<i>p</i> = 3.26E - 10), SIGLEC6 (<i>p</i> = 2.47E - 05), ISG15 (<i>p</i> = 3.69E - 05), and FCRL3 (<i>p</i> = 1.10E - 10) were identified as risk factors. B4GALT1 (<i>p</i> = 6.59E - 05) was associated with a lower risk of Type 1 diabetes (T1D). Interestingly, CTSH was identified as a protective factor for narcolepsy (<i>p</i> = 1.58E - 09) but a risk factor for T1D (<i>p</i> = 7.36E - 11), respectively. External validation supported the associations of eight of these proteins with three ADs.</p><p><strong>Conclusions: </strong>Our integrated study identified 12 potential therapeutic targets for ADs and provided novel insights into future drug development for ADs.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patients with systemic lupus erythematosus (SLE), a heterogeneous and chronic autoimmune disease, exhibit unique changes in the complex composition and transcriptional signatures of peripheral blood mononuclear cells (PBMCs). While the mechanism of pathogenesis for both childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) remains unclear, cSLE patients are considered more unpredictable and dangerous than aSLE patients. In this study, we analysed single-cell RNA sequencing data (scRNA-seq) to profile the PBMC clusters of cSLE/aSLE patients and matched healthy donors and compared the PBMC composition and transcriptional variations between the two groups. Our analysis revealed that the PBMC composition and transcriptional variations in cSLE patients were similar to those in aSLE patients. Comparative single-cell transcriptome analysis between healthy donors and SLE patients revealed IFITM3, ISG15, IFI16 and LY6E as potential therapeutic targets for both aSLE and cSLE patients. Additionally, we observed that the percentage of pre-B cells (CD34-) was increased in cSLE patients, while the percentage of neutrophil cells was upregulated in aSLE patients. Notably, we found decreased expression of TPM2 in cSLE patients, and similarly, TMEM150B, IQSEC2, CHN2, LRP8 and USP46 were significantly downregulated in neutrophil cells from aSLE patients. Overall, our study highlights the differences in complex PBMC composition and transcriptional profiles between cSLE and aSLE patients, providing potential biomarkers that could aid in diagnosing SLE.
{"title":"Single-cell analysis with childhood and adult systemic lupus erythematosus.","authors":"Jing Wang, Xiran Yang, Yanhua Zhang, Xuemei Jiang, Yanfang Li, Jingjing Cui, Yabin Liao","doi":"10.1080/08916934.2023.2281228","DOIUrl":"10.1080/08916934.2023.2281228","url":null,"abstract":"<p><p>Patients with systemic lupus erythematosus (SLE), a heterogeneous and chronic autoimmune disease, exhibit unique changes in the complex composition and transcriptional signatures of peripheral blood mononuclear cells (PBMCs). While the mechanism of pathogenesis for both childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) remains unclear, cSLE patients are considered more unpredictable and dangerous than aSLE patients. In this study, we analysed single-cell RNA sequencing data (scRNA-seq) to profile the PBMC clusters of cSLE/aSLE patients and matched healthy donors and compared the PBMC composition and transcriptional variations between the two groups. Our analysis revealed that the PBMC composition and transcriptional variations in cSLE patients were similar to those in aSLE patients. Comparative single-cell transcriptome analysis between healthy donors and SLE patients revealed IFITM3, ISG15, IFI16 and LY6E as potential therapeutic targets for both aSLE and cSLE patients. Additionally, we observed that the percentage of pre-B cells (CD34<sup>-</sup>) was increased in cSLE patients, while the percentage of neutrophil cells was upregulated in aSLE patients. Notably, we found decreased expression of TPM2 in cSLE patients, and similarly, TMEM150B, IQSEC2, CHN2, LRP8 and USP46 were significantly downregulated in neutrophil cells from aSLE patients. Overall, our study highlights the differences in complex PBMC composition and transcriptional profiles between cSLE and aSLE patients, providing potential biomarkers that could aid in diagnosing SLE.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-03-04DOI: 10.1080/08916934.2023.2259137
Sixian Bai, Hongyu Cheng, Hao Li, Peng Bo
Autophagy is implicated in the pathogenesis of psoriasis. We aimed to identify autophagy-related biomarkers in psoriasis via an integrated bioinformatics approach. We downloaded the gene expression profiles of GSE30999 dataset, and the "limma" package was applied to identify differentially expressed genes (DEGs). Then, differentially expressed autophagy-related genes (DEARGs) were identified via integrating autophagy-related genes with DEGs. CytoHubba plugin was used for the identification of hub genes and verified by the GSE41662 dataset. Subsequently, a series of bioinformatics analyses were employed, including protein-protein interaction network, functional enrichment, spearman correlation, receiver operating characteristic, and immune infiltration analyses. One hundred and one DEARGs were identified, and seven DEARGs were identified as hub genes and verified using the GSE41662 dataset. These validated genes had good diagnostic value in distinguishing psoriasis lesions. Immune infiltration analysis indicated that ATG5, SQSTM1, EGFR, MAPK8, MAPK3, MYC, and PIK3C3 were correlated with infiltration of immune cells. Seven DEARGs, namely ATG5, SQSTM1, EGFR, MAPK8, MAPK3, MYC, and PIK3C3, may be involved in the pathogenesis of psoriasis, which expanded the understanding of the development of psoriasis and provided important clinical significance for treatment of this disease.
{"title":"Integrated bioinformatics analysis identifies autophagy-associated genes as candidate biomarkers and reveals the immune infiltration landscape in psoriasis.","authors":"Sixian Bai, Hongyu Cheng, Hao Li, Peng Bo","doi":"10.1080/08916934.2023.2259137","DOIUrl":"10.1080/08916934.2023.2259137","url":null,"abstract":"<p><p>Autophagy is implicated in the pathogenesis of psoriasis. We aimed to identify autophagy-related biomarkers in psoriasis <i>via</i> an integrated bioinformatics approach. We downloaded the gene expression profiles of GSE30999 dataset, and the \"limma\" package was applied to identify differentially expressed genes (DEGs). Then, differentially expressed autophagy-related genes (DEARGs) were identified <i>via</i> integrating autophagy-related genes with DEGs. CytoHubba plugin was used for the identification of hub genes and verified by the GSE41662 dataset. Subsequently, a series of bioinformatics analyses were employed, including protein-protein interaction network, functional enrichment, spearman correlation, receiver operating characteristic, and immune infiltration analyses. One hundred and one DEARGs were identified, and seven DEARGs were identified as hub genes and verified using the GSE41662 dataset. These validated genes had good diagnostic value in distinguishing psoriasis lesions. Immune infiltration analysis indicated that ATG5, SQSTM1, EGFR, MAPK8, MAPK3, MYC, and PIK3C3 were correlated with infiltration of immune cells. Seven DEARGs, namely ATG5, SQSTM1, EGFR, MAPK8, MAPK3, MYC, and PIK3C3, may be involved in the pathogenesis of psoriasis, which expanded the understanding of the development of psoriasis and provided important clinical significance for treatment of this disease.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Our previous study found that Cullin 4B (CUL4B) inhibited rheumatoid arthritis (RA) pathology through glycogen synthase kinase-3beta (GSK3β)/canonical Wnt signalling pathway. In this work, pre-experiment and bioinformatics analysis suggested that circ_0011058 may lead to the up-regulation of CUL4B expression by inhibiting miR-335-5p. Therefore, we studied whether circ_0011058 can promote the expression of CUL4B through sponging the miR-335-5p and further promote the pathological development of RA. Bioinformatics prediction, real-time quantitative PCR (RT-qPCR), western blot (WB), double luciferase reporter gene and other relevant methods were used to study the inhibition of circ_0011058 on RA pathology and its molecular mechanism. Results showed that the expression of circ_0011058 was significantly increased in adjuvant arthritis (AA) rats and RA fibroblast-like synoviocytes (FLS). The knockout of circ_0011058 inhibited the proliferation of AA FLS and RA FLS, decreased the levels of interleukin-1 beta (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), and inhibited the expression of matrix metalloproteinase 3 (MMP3), fibronectin, which showed that circ_0011058 had a strong role in promoting RA pathology. Furthermore, miR-335-5p expression was reduced in AA rats and RA FLS. The highly expressed circ_0011058 directly sponged the miR-335-5p, which led to the increase of CUL4B expression and promoted the activation of the GSK3β/canonical signalling pathway. Finally, we confirmed that miR-335-5p mediated the roles of circ_0011058 in promoting RA pathological development, which showed that the circ_0011058/miR-335-5p/CUL4B signal axis was involved in RA pathology. This work was of great significance for clarifying the roles of circ_0011058 in RA pathology, and further work was needed to establish whether circ_0011058 was a potential therapeutic target or diagnostic marker for RA.
{"title":"Circ_0011058 alleviates RA pathology through the circ_0011058/miR-335-5p/CUL4B signal axis.","authors":"Xiaomei Wang, Qiuyun Xue, Qiangjun Duan, Ziyi Sun, Yajie Wu, Shuo Yang, Pengfei Xu, Huibo Cao, Faxue Liao, Xiao Wang, Chenggui Miao","doi":"10.1080/08916934.2023.2299587","DOIUrl":"10.1080/08916934.2023.2299587","url":null,"abstract":"<p><p>Our previous study found that Cullin 4B (CUL4B) inhibited rheumatoid arthritis (RA) pathology through glycogen synthase kinase-3beta (GSK3β)/canonical Wnt signalling pathway. In this work, pre-experiment and bioinformatics analysis suggested that circ_0011058 may lead to the up-regulation of CUL4B expression by inhibiting miR-335-5p. Therefore, we studied whether circ_0011058 can promote the expression of CUL4B through sponging the miR-335-5p and further promote the pathological development of RA. Bioinformatics prediction, real-time quantitative PCR (RT-qPCR), western blot (WB), double luciferase reporter gene and other relevant methods were used to study the inhibition of circ_0011058 on RA pathology and its molecular mechanism. Results showed that the expression of circ_0011058 was significantly increased in adjuvant arthritis (AA) rats and RA fibroblast-like synoviocytes (FLS). The knockout of circ_0011058 inhibited the proliferation of AA FLS and RA FLS, decreased the levels of interleukin-1 beta (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), and inhibited the expression of matrix metalloproteinase 3 (MMP3), fibronectin, which showed that circ_0011058 had a strong role in promoting RA pathology. Furthermore, miR-335-5p expression was reduced in AA rats and RA FLS. The highly expressed circ_0011058 directly sponged the miR-335-5p, which led to the increase of CUL4B expression and promoted the activation of the GSK3β/canonical signalling pathway. Finally, we confirmed that miR-335-5p mediated the roles of circ_0011058 in promoting RA pathological development, which showed that the circ_0011058/miR-335-5p/CUL4B signal axis was involved in RA pathology. This work was of great significance for clarifying the roles of circ_0011058 in RA pathology, and further work was needed to establish whether circ_0011058 was a potential therapeutic target or diagnostic marker for RA.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-02-29DOI: 10.1080/08916934.2023.2201412
Huiqing Yang, Yan Luo, Xiaofei Lai
Objective: To explore the effect of CD5-like molecule (CD5L) on rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS) and the relative molecular mechanism of CD5L in it.
Methods: Recombinant protein CD5L was used to stimulate the cultured RA-FLS cells. The inflammation-related cytokines were determined by real time-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The signal molecules and apoptosis-related molecules were detected by western blot assay (WB), and cell counting kit-8 (CCK-8) was used to detect the proliferation.
Results: CD5L can increase the production of IL-6, IL-8, and TNF-α and this effect can be inhibited by signal pathway inhibitor. At the same time, CD5L activated ERK1/2 MAPK signal, inhibitor treatment can weaken the intensity of phosphorylation. In addition, CD5L can enhance the proliferation ability of RA-FLS.
Conclusion: CD5L induces the production of inflammatory cytokines in RA-FLS through the ERK1/2 MAPK pathway and increases cell survival.
{"title":"CD5L induces inflammation and survival in RA-FLS through ERK1/2 MAPK pathway.","authors":"Huiqing Yang, Yan Luo, Xiaofei Lai","doi":"10.1080/08916934.2023.2201412","DOIUrl":"10.1080/08916934.2023.2201412","url":null,"abstract":"<p><strong>Objective: </strong>To explore the effect of CD5-like molecule (CD5L) on rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS) and the relative molecular mechanism of CD5L in it.</p><p><strong>Methods: </strong>Recombinant protein CD5L was used to stimulate the cultured RA-FLS cells. The inflammation-related cytokines were determined by real time-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The signal molecules and apoptosis-related molecules were detected by western blot assay (WB), and cell counting kit-8 (CCK-8) was used to detect the proliferation.</p><p><strong>Results: </strong>CD5L can increase the production of IL-6, IL-8, and TNF-α and this effect can be inhibited by signal pathway inhibitor. At the same time, CD5L activated ERK1/2 MAPK signal, inhibitor treatment can weaken the intensity of phosphorylation. In addition, CD5L can enhance the proliferation ability of RA-FLS.</p><p><strong>Conclusion: </strong>CD5L induces the production of inflammatory cytokines in RA-FLS through the ERK1/2 MAPK pathway and increases cell survival.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-02-08DOI: 10.1080/08916934.2024.2304826
Yinlan Wu, Yanhong Li, Yu Zhou, Xiufeng Bai, Yi Liu
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.
{"title":"Bioinformatics and systems-biology approach to identify common pathogenic mechanisms for COVID-19 and systemic lupus erythematosus.","authors":"Yinlan Wu, Yanhong Li, Yu Zhou, Xiufeng Bai, Yi Liu","doi":"10.1080/08916934.2024.2304826","DOIUrl":"10.1080/08916934.2024.2304826","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Result: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139705973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-06-13DOI: 10.1080/08916934.2024.2358069
Feige Nian, Yiwen Wang, Mingfeng Yang, Bin Zhang
Rheumatoid arthritis (RA) is the predominant manifestation of inflammatory arthritis, distinguished by an increasing burden of morbidity and mortality. The intricate interplay of genes and signalling pathways involved in synovial inflammation in patients with RA remains inadequately comprehended. This study aimed to ascertain the role of necroptosis in RA, as along with their associations with immune cell infiltration. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were employed to identify central genes for RA. In this study, identified total of 28 differentially expressed genes (DEGs) were identified in RA. Utilising WGCNA, two co-expression modules were generated, with one module demonstrating the strongest correlation with RA. Through the integration of differential gene expression analysis, a total of 5 intersecting genes were discovered. These 5 hub genes, namely fused in sarcoma (FUS), transformer 2 beta homolog (TRA2B), eukaryotic translation elongation factor 2 (EEF2), cleavage and polyadenylation specific factor 6 (CPSF6) and signal transducer and activator of transcription 3 (STAT3) were found to possess significant diagnostic value as determined by receiver operating characteristic (ROC) curve analysis. The close association between the concentrations of various immune cells is anticipated to contribute to the diagnosis and treatment of RA. Furthermore, the infiltration of immune cells mentioned earlier is likely to exert a substantial influence on the initiation of this disease.
类风湿性关节炎(RA)是炎症性关节炎的主要表现形式,其发病率和死亡率不断上升。目前,人们对参与类风湿性关节炎患者滑膜炎症的基因和信号通路之间错综复杂的相互作用仍缺乏足够的了解。本研究旨在确定坏死在 RA 中的作用及其与免疫细胞浸润的关系。研究采用了差异表达分析和加权基因共表达网络分析(WGCNA)来确定 RA 的中心基因。在这项研究中,共鉴定出 28 个差异表达基因(DEGs)。利用 WGCNA,生成了两个共表达模块,其中一个模块与 RA 的相关性最强。通过整合差异基因表达分析,共发现了 5 个交叉基因。通过接收者操作特征曲线(ROC)分析,发现这5个枢纽基因,即肉瘤融合基因(FUS)、变压器2β同源基因(TRA2B)、真核翻译伸长因子2(EEF2)、裂解和多腺苷酸化特异性因子6(CPSF6)以及信号转导和转录激活因子3(STAT3)具有显著的诊断价值。各种免疫细胞浓度之间的密切联系预计将有助于 RA 的诊断和治疗。此外,前面提到的免疫细胞浸润很可能对该病的发病产生重大影响。
{"title":"Identification the role of necroptosis in rheumatoid arthritis by WGCNA network.","authors":"Feige Nian, Yiwen Wang, Mingfeng Yang, Bin Zhang","doi":"10.1080/08916934.2024.2358069","DOIUrl":"https://doi.org/10.1080/08916934.2024.2358069","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is the predominant manifestation of inflammatory arthritis, distinguished by an increasing burden of morbidity and mortality. The intricate interplay of genes and signalling pathways involved in synovial inflammation in patients with RA remains inadequately comprehended. This study aimed to ascertain the role of necroptosis in RA, as along with their associations with immune cell infiltration. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were employed to identify central genes for RA. In this study, identified total of 28 differentially expressed genes (DEGs) were identified in RA. Utilising WGCNA, two co-expression modules were generated, with one module demonstrating the strongest correlation with RA. Through the integration of differential gene expression analysis, a total of 5 intersecting genes were discovered. These 5 hub genes, namely fused in sarcoma (FUS), transformer 2 beta homolog (TRA2B), eukaryotic translation elongation factor 2 (EEF2), cleavage and polyadenylation specific factor 6 (CPSF6) and signal transducer and activator of transcription 3 (STAT3) were found to possess significant diagnostic value as determined by receiver operating characteristic (ROC) curve analysis. The close association between the concentrations of various immune cells is anticipated to contribute to the diagnosis and treatment of RA. Furthermore, the infiltration of immune cells mentioned earlier is likely to exert a substantial influence on the initiation of this disease.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-08-21DOI: 10.1080/08916934.2024.2387414
Kyle R Pressley, Lance Schwegman, Maria Montes De Oca Arena, Carol Chase Huizar, Scott S Zamvil, Thomas G Forsthuber
It is known that certain human leukocyte antigen (HLA) genes are associated with autoimmune central nervous system (CNS) diseases, such as multiple sclerosis (MS), but their exact role in disease susceptibility and etiopathogenesis remains unclear. The best studied HLA-associated autoimmune CNS disease is MS, and thus will be the primary focus of this review. Other HLA-associated autoimmune CNS diseases, such as autoimmune encephalitis and neuromyelitis optica will be discussed. The lack of animal models to accurately capture the complex human autoimmune response remains a major challenge. HLA transgenic (tg) mice provide researchers with powerful tools to investigate the underlying mechanisms promoting susceptibility and progression of HLA-associated autoimmune CNS diseases, as well as for elucidating the myelin epitopes potentially targeted by T cells in autoimmune disease patients. We will discuss the potential role(s) of autoimmune disease-associated HLA alleles in autoimmune CNS diseases and highlight information provided by studies using HLA tg mice to investigate the underlying pathological mechanisms and opportunities to use these models for development of novel therapies.
{"title":"HLA-transgenic mouse models to study autoimmune central nervous system diseases.","authors":"Kyle R Pressley, Lance Schwegman, Maria Montes De Oca Arena, Carol Chase Huizar, Scott S Zamvil, Thomas G Forsthuber","doi":"10.1080/08916934.2024.2387414","DOIUrl":"10.1080/08916934.2024.2387414","url":null,"abstract":"<p><p>It is known that certain human leukocyte antigen (HLA) genes are associated with autoimmune central nervous system (CNS) diseases, such as multiple sclerosis (MS), but their exact role in disease susceptibility and etiopathogenesis remains unclear. The best studied HLA-associated autoimmune CNS disease is MS, and thus will be the primary focus of this review. Other HLA-associated autoimmune CNS diseases, such as autoimmune encephalitis and neuromyelitis optica will be discussed. The lack of animal models to accurately capture the complex human autoimmune response remains a major challenge. HLA transgenic (<i>tg</i>) mice provide researchers with powerful tools to investigate the underlying mechanisms promoting susceptibility and progression of HLA-associated autoimmune CNS diseases, as well as for elucidating the myelin epitopes potentially targeted by T cells in autoimmune disease patients. We will discuss the potential role(s) of autoimmune disease-associated <i>HLA</i> alleles in autoimmune CNS diseases and highlight information provided by studies using HLA <i>tg</i> mice to investigate the underlying pathological mechanisms and opportunities to use these models for development of novel therapies.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-07-08DOI: 10.1080/08916934.2024.2370536
Lauren K Heine, Lichchavi D Rajasinghe, James G Wagner, Ryan P Lewandowski, Quan-Zhen Li, Alexa L Richardson, Ashleigh N Tindle, Jenan J Shareef, Jack R Harkema, James J Pestka
Lupus, a systemic autoimmune disease shaped by gene-environment interplay, often progresses to endstage renal failure. While subchronic systemic exposure to bacterial lipopolysaccharide (LPS) triggers autoimmunity and glomerulonephritis in lupus-prone mice, it is unknown if inhaling LPS, which is common in certain occupations, can similarly trigger lupus. Here we determined how subchronic intranasal (IN) LPS instillation influences autoimmunity and glomerulonephritis development in lupusprone NZBWF1 female mice. Briefly, mice were IN-instilled with vehicle or E. coli LPS (0.8 μg/g) twice weekly for 5 wk, followed by necropsy. For systemic comparison, additional cohorts of mice were injected with LPS intraperitoneally (IP) using identical doses/timing. Lungs were assessed for inflammatory and autoimmune responses and then related to systemic autoimmunity and glomerulonephritis. IN/LPS exposure induced in the lung: i) leukocyte infiltration, ii)mRNA signatures for cytokines, chemokines, IFN-regulated, and cell death-related genes, iii) ectopic lymphoid tissue formation, and iv)diverse IgM and IgG autoantibodies (AAbs). Pulmonary effects coincided with enlarged spleens, elevated plasma IgG AAbs, and inflamed IgG-containing kidney glomeruli. In contrast, IP/LPS treatment induced systemic autoimmunity and glomerulonephritis without pulmonary manifestations. Taken together, these preclinical findings suggest the lung could serve as a critical nexus for triggering autoimmunity by respirable LPS in genetically predisposed individuals.
{"title":"Subchronic intranasal lipopolysaccharide exposure induces pulmonary autoimmunity and glomerulonephritis in NZBWF1 mice.","authors":"Lauren K Heine, Lichchavi D Rajasinghe, James G Wagner, Ryan P Lewandowski, Quan-Zhen Li, Alexa L Richardson, Ashleigh N Tindle, Jenan J Shareef, Jack R Harkema, James J Pestka","doi":"10.1080/08916934.2024.2370536","DOIUrl":"10.1080/08916934.2024.2370536","url":null,"abstract":"<p><p>Lupus, a systemic autoimmune disease shaped by gene-environment interplay, often progresses to endstage renal failure. While subchronic systemic exposure to bacterial lipopolysaccharide (LPS) triggers autoimmunity and glomerulonephritis in lupus-prone mice, it is unknown if inhaling LPS, which is common in certain occupations, can similarly trigger lupus. Here we determined how subchronic intranasal (IN) LPS instillation influences autoimmunity and glomerulonephritis development in lupusprone NZBWF1 female mice. Briefly, mice were IN-instilled with vehicle or E. coli LPS (0.8 μg/g) twice weekly for 5 wk, followed by necropsy. For systemic comparison, additional cohorts of mice were injected with LPS intraperitoneally (IP) using identical doses/timing. Lungs were assessed for inflammatory and autoimmune responses and then related to systemic autoimmunity and glomerulonephritis. IN/LPS exposure induced in the lung: i) leukocyte infiltration, ii)mRNA signatures for cytokines, chemokines, IFN-regulated, and cell death-related genes, iii) ectopic lymphoid tissue formation, and iv)diverse IgM and IgG autoantibodies (AAbs). Pulmonary effects coincided with enlarged spleens, elevated plasma IgG AAbs, and inflamed IgG-containing kidney glomeruli. In contrast, IP/LPS treatment induced systemic autoimmunity and glomerulonephritis without pulmonary manifestations. Taken together, these preclinical findings suggest the lung could serve as a critical nexus for triggering autoimmunity by respirable LPS in genetically predisposed individuals.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-06-08DOI: 10.1080/08916934.2024.2361745
Eroboghene E Ubogu
Immune-mediated demyelinating polyneuropathies (IMDPs) are rare disorders in which dysregulated adaptive immune responses cause peripheral nerve demyelinating inflammation and axonal injury in susceptible individuals. Despite significant advances in understanding IMDP pathogenesis guided by patient data and representative mammalian models, specific therapies are lacking. Significant knowledge gaps in IMDP pathogenesis still exist, e.g. precise antigen(s) and mechanisms that initially trigger immune system activation and identification of large population disease susceptibility factors. The initial directional cues for antigen-specific effector or autoreactive leukocyte trafficking into peripheral nerves are also unknown. An overview of current animal models, with emphasis on the experimental autoimmune neuritis and spontaneous autoimmune peripheral polyneuropathy models, is provided. Insights on the initial directional cues for peripheral nerve tissue specific autoimmunity using a novel Major Histocompatibility Complex class II conditional knockout mouse strain are also discussed, suggesting an essential research tool to study cell- and time-dependent adaptive immunity in autoimmune diseases.
免疫介导的脱髓鞘性多发性神经病(IMDPs)是一种罕见疾病,在这种疾病中,适应性免疫反应失调会导致易感个体出现周围神经脱髓鞘炎症和轴突损伤。尽管在患者数据和代表性哺乳动物模型的指导下,人们在了解 IMDP 发病机制方面取得了重大进展,但仍缺乏特异性疗法。在 IMDP 发病机制方面仍然存在重大的知识空白,例如最初触发免疫系统激活的精确抗原和机制,以及大量人群疾病易感因素的识别。抗原特异性效应细胞或自体反应性白细胞进入周围神经的最初定向线索也尚不清楚。本文概述了当前的动物模型,重点是实验性自身免疫性神经炎和自发性自身免疫性周围多发性神经病模型。此外,还讨论了利用新型主要组织相容性复合物 II 类条件性基因敲除小鼠品系对周围神经组织特异性自身免疫最初定向线索的见解,这表明这是研究自身免疫性疾病中细胞和时间依赖性适应性免疫的重要研究工具。
{"title":"Animal models of immune-mediated demyelinating polyneuropathies.","authors":"Eroboghene E Ubogu","doi":"10.1080/08916934.2024.2361745","DOIUrl":"10.1080/08916934.2024.2361745","url":null,"abstract":"<p><p>Immune-mediated demyelinating polyneuropathies (IMDPs) are rare disorders in which dysregulated adaptive immune responses cause peripheral nerve demyelinating inflammation and axonal injury in susceptible individuals. Despite significant advances in understanding IMDP pathogenesis guided by patient data and representative mammalian models, specific therapies are lacking. Significant knowledge gaps in IMDP pathogenesis still exist, e.g. precise antigen(s) and mechanisms that initially trigger immune system activation and identification of large population disease susceptibility factors. The initial directional cues for antigen-specific effector or autoreactive leukocyte trafficking into peripheral nerves are also unknown. An overview of current animal models, with emphasis on the experimental autoimmune neuritis and spontaneous autoimmune peripheral polyneuropathy models, is provided. Insights on the initial directional cues for peripheral nerve tissue specific autoimmunity using a novel Major Histocompatibility Complex class II conditional knockout mouse strain are also discussed, suggesting an essential research tool to study cell- and time-dependent adaptive immunity in autoimmune diseases.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}