Widely varying TNF-α levels in patients with myasthenia gravis

Lee, Jin Soo; Joo, In Soo; Seok, Jung Im

doi:10.1007/s10072-009-0023-0

Cited by 11 publications

(6 citation statements)

References 14 publications

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“…In previous years, a number of risk genes of MG have been identified, including circulating interleukin (IL)-17A, which was identified to be increased in patients with MG compared with normal controls, and increases of IL-17A were associated with general muscle weakness (3). Tumor necrosis factor-α (TNF-α) is considered to be one of the most important cytokines in the pathogenesis of autoimmune MG, and the inhibition of TNF-α may have significant clinical efficacy for MG (4). Furthermore, chemokine CC motif receptor (CCR) 9 and CCR7 have been demonstrated to be abnormally expressed at different thymocyte stages of MG, and the overexpression of CCR9 and CCR7 in CD4-CD8-double negative thymocytes is associated with abnormal intrathymic T-cell differentiation in patients with MG (5).…”

Section: Introductionmentioning

confidence: 99%

Global pathway view analysis of microRNA clusters in myasthenia gravis

Wang

Zhang

et al. 2019

Mol Med Report

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The significant roles of microRNAs (miRNAs) in the pathogenesis of myasthenia gravis (MG) have been observed in numerous previous studies. The impact of miRNA clusters on immunity has been demonstrated in previous years; however, the regulation of miRNA clusters in MG remains to be elucidated. In the present study, 245 MG risk genes were collected and 99 MG risk pathways enriched by these genes were identified. A catalog of 126 MG risk miRNAs was then created; the MG risk miRNAs were located on each chromosome and a miRNA cluster was defined as a number of miRNAs with a relative distance of <6 kb on the same sub-band, same band, same region and same chromosome. Furthermore, enrichment analyses were performed using the target genes of the MG risk miRNA clusters, and a number of risk pathways of each miRNA clusters were identified. As a result, 15 significant miRNA clusters associated with MG were identified. Additionally, the most significant pathways of the miRNA clusters were identified to be enriched on chromosomes 9, 19 and 22, characterized by immunity, infection and carcinoma, suggesting that the mechanism of MG may be associated with certain abnormalities of miRNA clusters on chromosomes 9, 19 and 22. The present study provides novel insight into a global pathway view of miRNA clusters in the pathogenesis of MG.

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Section: Introductionmentioning

confidence: 99%

Global pathway view analysis of microRNA clusters in myasthenia gravis

Wang

Zhang

et al. 2019

Mol Med Report

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“…6 It has been evidenced to act as a critical role in the MG pathogenesis, and TNF-α-blocking agents have shown significant clinical efficacy and are proposed for MG treatment. 7 TNF-α gene promoter polymorphisms have been demonstrated to be closely linked with disease pathology. To list a few, TNF-α -1031T/C and -863C/A polymorphisms are closely associated with the risk, clinical manifestation and progression of thyroid-associated ophthalmopathy (TAO).…”

Section: Introductionmentioning

confidence: 99%

Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population

Lei

Xie

et al. 2017

Cancer Gene Ther

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This study was performed with the aim to investigate the correlations of tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population. Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG group) and 293 healthy volunteers (negative control (NC) group) were enrolled in this study. Among the MG patients, there were 121 patients with thymoma-associated MG (T-MG group) and 184 without T-MG (NT-MG group). Enzyme-linked immunosorbent assay (ELISA) was used for the serum TNF-α level. Polymerase chain reaction-restriction fragment length polymorphism was conducted to determine genotype and allele frequencies of TNF-α gene promoter -1031T/C, -857C/T and -863C/A. The haplotype was analyzed with the SHEsis software. Logistic regression analysis was performed for correlations between TNF-α gene promoter polymorphisms and the risk of T-MG. The T-MG group had higher frequencies of the CT/TT genotype and T allele of -857C/T than the NT-MG and NC groups. The frequencies of the CC genotype and C allele of -1031T/C were higher in the T-MG group than in the NT-MG and NC groups, and higher in male patients in the T-MG group than in male patients in the NC group. TTA and TTC haplotypes exhibited lower frequencies in the T-MG group than in the NT-MG group. The ocular MG patients exhibited lower frequencies of the TT genotype and T allele of -857C/T than the generalized MG patients did. The TNF-α level was elevated in the T-MG group compared with that in the NC and NT-MG groups, indicating that the TC+CC and CT+TT genotypes were increased compared with the TT and CC genotypes in the -1031T/C and -857C/T, respectively. Logistic regression analysis suggested that expressions of anti-acetylcholine receptor antibodies, Osserman's classification, -1031T/C and -857C/T polymorphisms and the TTA haplotype were the independent risk factors for T-MG. These findings reveal that TNF-α -1031T/C and -857C/T polymorphisms and the TTA haplotype may be correlated with the occurrence of T-MG in a Northern Chinese Han population.

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“…However, MG is mainly caused by thymoma and may also be related to other kind of cancers, which implies that GO functions may be key factors for the treatment of MG. We can see that GO term of GO:0051092 was associated with all of the candidate drugs through TNF . A study showed that TNF was one of the most important cytokines in the mechanism of MG, and inhibiting TNF may exert notable clinical efficacy for MG [43], which indicates that TNF may be a significant therapeutic target in the future. We summarized the information on target genes among the 5 candidate drugs and immune-unrelated GO functions in S4 Table.…”

Section: Resultsmentioning

confidence: 99%

Building the drug-GO function network to screen significant candidate drugs for myasthenia gravis

Cao

et al. 2019

PLoS ONE

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Myasthenia gravis (MG) is an autoimmune disease. In recent years, considerable evidence has indicated that Gene Ontology (GO) functions, especially GO-biological processes, have important effects on the mechanisms and treatments of different diseases. However, the roles of GO functions in the pathogenesis and treatment of MG have not been well studied. This study aimed to uncover the potential important roles of risk-related GO functions and to screen significant candidate drugs related to GO functions for MG. Based on MG risk genes, 238 risk GO functions and 42 drugs were identified. Through constructing a GO function network, we discovered that positive regulation of NF-kappaB transcription factor activity (GO:0051092) may be one of the most important GO functions in the mechanism of MG. Furthermore, we built a drug-GO function network to help evaluate the latent relationship between drugs and GO functions. According to the drug-GO function network, 5 candidate drugs showing promise for treating MG were identified. Indeed, 2 out of 5 candidate drugs have been investigated to treat MG. Through functional enrichment analysis, we found that the mechanisms between 5 candidate drugs and associated GO functions may involve two vital pathways, specifically hsa05332 (graft-versus-host disease) and hsa04940 (type I diabetes mellitus). More interestingly, most of the processes in these two pathways were consistent. Our study will not only reveal a new perspective on the mechanisms and novel treatment strategies of MG, but also will provide strong support for research on GO functions.

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Widely varying TNF-α levels in patients with myasthenia gravis

Cited by 11 publications

References 14 publications

Global pathway view analysis of microRNA clusters in myasthenia gravis

Global pathway view analysis of microRNA clusters in myasthenia gravis

Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population

Building the drug-GO function network to screen significant candidate drugs for myasthenia gravis

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