Myasthenia Gravis: An Acquired Interferonopathy?

Payet, Christine; You, Axel; Fayet, Odessa-Maud; Dragin, Nadine; Berrih‐Aknin, Sonia; Panse, Rozen Le

doi:10.3390/cells11071218

Cited by 17 publications

(11 citation statements)

References 130 publications

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“…It has also been shown that oxidative stress and low antioxidant status play a major role in the pathogenesis of inflammatory and autoimmune diseases, and that MG patients with low antioxidant status have active oxidative processes ( Yang et al, 2016 ; Adamczyk-Sowa et al, 2017 ). In addition to this, studies have confirmed that AChR-MG may be an acquired interferon disease ( Payet et al, 2022 ). The results of GO and KEGG analysis in this study also suggest that MG dysregulated genes are mainly enriched in interferon and immune-related processes.…”

Section: Discussionmentioning

confidence: 74%

Transcriptional landscape of myasthenia gravis revealed by weighted gene coexpression network analysis

et al. 2023

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Background: As one of the most common autoimmune diseases, myasthenia gravis (MG) severely affects the quality of life of patients. Therefore, exploring the role of dysregulated genes between MG and healthy controls in the diagnosis of MG is beneficial to reveal new and promising diagnostic biomarkers and clinical therapeutic targets.Methods: The GSE85452 dataset was downloaded from the Gene Expression Omnibus (GEO) database and differential gene expression analysis was performed on MG and healthy control samples to identify differentially expressed genes (DEGs). The functions and pathways involved in DEGs were also explored by functional enrichment analysis. Significantly associated modular genes were identified by weighted gene co-expression network analysis (WGCNA), and MG dysregulated gene co-expression modular-based diagnostic models were constructed by gene set variance analysis (GSVA) and least absolute shrinkage and selection operator (LASSO). In addition, the effect of model genes on tumor immune infiltrating cells was assessed by CIBERSORT. Finally, the upstream regulators of MG dysregulated gene co-expression module were obtained by Pivot analysis.Results: The green module with high diagnostic performance was identified by GSVA and WGCNA. The LASSO model obtained NAPB, C5orf25 and ERICH1 genes had excellent diagnostic performance for MG. Immune cell infiltration results showed a significant negative correlation between green module scores and infiltration abundance of Macrophages M2 cells.Conclusion: In this study, a diagnostic model based on the co-expression module of MG dysregulated genes was constructed, which has good diagnostic performance and contributes to the diagnosis of MG.

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Section: Discussionmentioning

confidence: 74%

Transcriptional landscape of myasthenia gravis revealed by weighted gene coexpression network analysis

et al. 2023

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“…Our results showed the target genes STAT1, MCL1, and FOS were upregulated in all cell subsets, and their abundance changed significantly from the normal control and pre-treatment group compared to their levels after treatment, indicating their importance in the remission of MG. STATs are also downstream targets of Janus tyrosine kinases, and the Janus tyrosine kinase/STAT signal transduction pathway mediates a variety of immune-related cytokine signals ( 23 , 24 ). Among these, the type-I interferon (IFN-I) signaling pathway depends on the induction of STAT1 ( 25 ), and IFN-I has been found to increase the risk of MG ( 26 ). Patients with MG exhibit high levels of IFN-I and expression of various IFN-I-induced genes in the thymus ( 27 ), and targeted STAT1 therapy may hold promise for its treatment.…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis

Liu¹,

Qi²,

Gu³

et al. 2022

Transl Pediatr

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Background: Myasthenia gravis (MG) is an acquired autoimmune disease of the neuromuscular junction.As immunosuppressive agents used to treat MG have a significant impact on the growth and development of children, treatment is extremely challenging. Jianpi Yiqi Bugan Yishen Decoction (JYBYD) has been developed to treat MG and has achieved satisfactory results in clinical practice. This study aimed to explore its action mechanism and evaluate its active ingredients and potential therapeutic targets.Methods: Single-cell transcriptome sequencing of peripheral blood immune cells of children with MG was performed to reveal the changes in immune cell profiles before and after JYBYD treatment. Lewis rats were included in the model, with classic MG induced by subcutaneous injection of the immunogen acetylcholine receptor (AChR). Twenty rats were divided into two groups and administered normal saline and JYBYD by gavage daily.Results: An increase in cell populations characterized by cortactin expression was observed, which has a potential effect on the recovery of lesions at the neuromuscular junction in patients with MG. Based on the differential expression of genes in various immune cells and the predicted targets of traditional Chinese medicine (TCM) compounds, the possible therapeutic targets of JYBYD in different cell subsets were identified, among which STAT1, MCL1, and FOS were the most frequent. Comprehensive network pharmacological analysis suggested quercetin, luteolin, and resveratrol as important active ingredients of JYBYD for the treatment of children with MG. JYBYD could relieve myasthenia symptoms and reduce the AChR-Ab titer in the rat model. Immunohistochemistry results of the muscle showed that JYBYD treatment decreased the expression of STAT1, MCL1, and c-FOS proteins in the muscles of MG rat models. Conclusions:The results of this study are of significance for the clinical application of JYBYD and drug development against MG in children.

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“…[12] The disease has a bimodal incidence pattern, affecting individuals of all ages but with a higher incidence among young women and elderly men. [13][14][15][16] While the pathogenesis of MG remains unclear, [17,18] available therapies for the condition include cholinesterase inhibitors, glucocorticoids, immunosuppressants, intravenous immunoglobulins, plasma exchange, and thymectomy. [19][20][21][22] Emerging treatment options for MG include hematopoietic stem cell transplantation and targeted biologics, such as eculizumab and rituximab, which diversified the available treatment portfolio for MG patients.…”

Section: Introductionmentioning

confidence: 99%

Global research hotspots and frontiers of myasthenia gravis from 2002 to 2021: A bibliometric study

Yang

Wu²,

Han

et al. 2023

Medicine

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The objective of this study is to utilize bibliometric and visual analysis techniques to identify hotspots and frontiers of research in myasthenia gravis (MG) and provide valuable references for future research. The Web of Science Core Collection (WoSCC) database was used to retrieve literature data related to MG research, which was then analyzed using VOSviewer 1.6.18, CiteSpace 6.1.R3, and the Online Platform for Bibliometric Analysis. The analysis revealed 6734 publications distributed across 1612 journals and contributed by as many as 24,024 authors affiliated with 4708 institutions across 107 countries/regions. The number of annual publications and citations for MG research has steadily increased over the past 2 decades, with the last 2 years alone witnessing a remarkable increase in annual publications and citations to over 600 and 17,000, respectively. In terms of productivity, the United States emerged as the top producing country, while the University of Oxford ranked first in terms of research institutions. Vincent A was identified as the top contributor in terms of publications and citations. Muscle & Nerve and Neurology ranked first in publications and citations respectively, with clinical neurology and neurosciences among the main subject categories explored. The study also identified pathogenesis, eculizumab, thymic epithelial cells, immune checkpoint inhibitors, thymectomy, MuSK antibodies, risk, diagnosis, and management as the current hot research topics in MG, while burst keywords like quality of life, immune-related adverse events (irAEs), rituximab, safety, nivolumab, cancer, and classification indicated the frontiers of MG research. This study effectively identifies the hotspots and frontiers of MG research, and offers valuable references for researchers interested in this area.

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Myasthenia Gravis: An Acquired Interferonopathy?

Cited by 17 publications

References 130 publications

Transcriptional landscape of myasthenia gravis revealed by weighted gene coexpression network analysis

Transcriptional landscape of myasthenia gravis revealed by weighted gene coexpression network analysis

Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis

Global research hotspots and frontiers of myasthenia gravis from 2002 to 2021: A bibliometric study

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