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Significance of B10 cell in patients with thymoma complicated with myasthenia gravis.

ABSTRACT: A subset of regulatory B cells in humans has been identified as B10 cell which has the function of secreting interleukin-10. We evaluated the significance of B10 cell in patients with thymoma complicated with myasthenia gravis. In this study, 156 patients diagnosed with thymoma were enrolled, FCM was used to detected the percentage of Breg/CD19+B cells and CD19+B cells/PBMC, ELISA to evaluate the serum concentration of the relevant immunological markers; purified CD19+B cells in tissues by MACS; gene and protein expressions of CD19 and IL-10 by Real-time PCR and Western-Blot; double immunofluorescence staining to detect the distribution of CD19 and IL-10 in thymus tissues. Thymoma patients without MG mainly display the types A and AB of thymoma, whereas the thymoma patients with MG mainly display type B (B1, B2 and B3) thymoma; AChR-Ab in Tm + MG group was the highest, with the progress of the disease, the percentage of Breg/CD19+B cells increased and B10/CD19+B cells decreased (p < 0.05); ROC curve showed that B10 had the greatest significance for the clinical directivity of Tm+MG and cut-off point = 0.55%; in accordance with the Con, Tm and Tm+MG group, the content of CD19+IL-10+B10 cells increased gradually (p < 0.05); meanwhile, the gene and protein expression levels of CD19 and IL-10 gradually increased in the same way. It is concluded that with the progress of thymoma, the infiltration of Breg in tumour tissue increases; however, as the severity of MG increases, the function of Breg (B10 cell) in peripheral blood decreases and the cut-off point is 0.55%.

SUBMITTER: Lu Y

PROVIDER: S-EPMC5650299 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Significance of B10 cell in patients with thymoma complicated with myasthenia gravis.

Lu Yang Y Meng Fanjie F Yang Yang Y Li Lan L Wang Donghao D Cui Yuantao Y Dong Shangwen S Wang Wanhua W

Oncotarget 20170517 43

A subset of regulatory B cells in humans has been identified as B10 cell which has the function of secreting interleukin-10. We evaluated the significance of B10 cell in patients with thymoma complicated with myasthenia gravis. In this study, 156 patients diagnosed with thymoma were enrolled, FCM was used to detected the percentage of Breg/CD19+B cells and CD19+B cells/PBMC, ELISA to evaluate the serum concentration of the relevant immunological markers; purified CD19+ ...[more]

PMID: 29088744

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Project description:Background: Approximately 50% of thymoma patients also show myasthenia gravis (MG), which is an autoimmune disease; however, the pathogenesis of MG-associated thymoma remains elusive. Our aim was to investigate immune-related lncRNA profiles of a set of candidate genes for better understanding of the molecular mechanism underlying the pathogenesis of thymoma with or without MG. Methods: Molecular profiles of thymoma with or without MG were downloaded from The Cancer Genome Atlas, and Pearson's correlation analysis was performed to identify immune-related lncRNAs. T test was used to examine the differential expression and differential methylation between thymoma patients with or without MG. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to predict the function of target genes of immune-related lncRNAs. Results: Analyses of the 87 thymoma samples with complete MG information revealed that 205 mRNAs and 56 lncRNAs showed up-regulated expression in thymoma with MG patients, while 458 mRNAs and 84 lncRNAs showed down-regulated expression. The methylation level of three immune-related lncRNAs (AP000787.1, AC004943.1, WT1-AS, FOXG1-AS1) was significantly decreased in thymoma tissues, and the methylation level of these immune-related lncRNAs (WT1-AS: Cor = 0.368, p < 0.001; FOXG1-AS1: Cor = 0.288, p < 0.01; AC004943.1: Cor = -0.236, p < 0.05) correlated with their expression. GO and KEGG pathway analysis revealed that targets of the immune-related lncRNA FOXG1-AS1 were enriched in small GTPase binding and herpes simplex virus 1 infection. Transcription coregulator activity and cell cycle were the most enriched pathways for targets of lncRNA AC004943.1. LncRNA WT1-AS targets were most enriched in actin binding and axon guidance. Conclusion: Our results revealed the immune-related molecular profiling of thymoma with MG and without MG and identified key pathways involved in the underlying molecular mechanism of thymoma-related MG. These findings provide insights for further research of potential markers for thymoma-related MG.

Project description:Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, whose clinical hallmark is muscle weakness and early fatigability. Azathioprine (AZA) is commonly used in Myasthenia Gravis therapy. AZA is a purine antagonist, which inhibits the cell cycle in the resting and DNA synthesis phases. It is usually used as an immunosuppressant to block T- and B-cell proliferation. AZA, bioconverted to 6-mercaptopurine by glutathione S-transferase (GST), can be metabolized either through the hypoxanthine phosphoribosyl transferase pathway to active 6-thioguanine nucleotides (6-TGN) or through the thiopurine S-methyltransferase (TPMT) pathway to inactive methyl-thiopurine metabolites. The incorporation of active 6-TGNs into DNA, causing breaks in DNA strands resulting in interference with RNA production and thereby protein synthesis, is responsible for the drug effect. The response to AZA is determined by which metabolic pathway is being favored. While balanced use of both HPRT and TPMT pathways results in responsiveness to AZA, hyperactivity of TPMT skews the balance towards the TPMT pathway and results in unresponsiveness to AZA with no pharmacological effect. In contrast, low TPMT activity skews the balance towards the HPRT pathway, resulting in increasing side-effects due to the accumulation of 6-TGNs. Current treatments for MG therapy are often inadequate because less than 40% of patients achieve complete remission with available drugs. This reflects the lack of drugs acting on target sites for which there is strong evidence of pathogenicity and the inability to identify responder patients. No criteria for responsiveness are available, exposing patients to unpredictable failures and unpredictable side effects. These individuals are at particular risk for adverse drug reaction (ADRs) or therapeutic failure. Genetic profiling with the Affymetrix drug metabolizing enzymes and transports genotyping array offers the ability to determine 1,931 variants and 225 genes involved in drug metabolism and disposition. Accordingly, the study of well-known drug-metabolizing genes can be involved in the specific metabolic pathway of a drug, which is more likely to define genotype-phenotype association and thereby genotype profiles relevant to drug response that can be applied as predictive biomarkers for pharmacological treatment.

Dataset Information

Significance of B10 cell in patients with thymoma complicated with myasthenia gravis.

Publications

Significance of B10 cell in patients with thymoma complicated with myasthenia gravis.

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