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Defects of CTLA-4 Are Associated with Regulatory T Cells in Myasthenia Gravis Implicated by Intravenous Immunoglobulin Therapy
Joint Authors
Xu, Wenhua
Ren, Mingshan
Ghosh, Swagata
Qian, Kai
Luo, Zhaofeng
Zhang, Aimei
Zhang, Cuiping
Cui, Jiajun
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-02-14
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Myasthenia gravis (MG) is a CD4+ T cell-dependent autoimmune disease resulting from aberrant immune response mediated by circulating autoantibodies at the neuromuscular junction.
Intravenous immunoglobulin (IVIg) is an expensive and commonly used immunotherapeutic approach to treat patients with MG.
The mechanisms of actions involved in IVIg treatment, however, remain to be investigated.
In an effort to examine the roles of various subsets of CD4+ T cells in the periphery blood of MG and uncover the mechanisms that contribute to the therapeutical effects of IVIg, we first demonstrated that a subset of CD4+ T cells, CTLA-4-expressing regulatory T (Treg) cells, were underrepresented and functionally defective in MG patients.
The dynamic profiling during the IVIg therapy course further revealed an inverse relationship between the frequency of CTLA-4+ Treg and the quantitative MG (QMG) score that represents disease severity.
Our mechanistic studies indicated that IVIg expands CTLA-4-Treg cells via modulating antigen-presenting dendritic cells (DCs).
To determine the molecular defects of CTLA-4 in abnormities of Treg in MG patients, we demonstrated hypermethylation at -658 and -793 CpGs of CTLA-4 promoter in MG Tregs.
Interestingly, IVIg therapy significantly reduced the methylation level at these two sites in MG patients.
Overall, our study may suggest a role of CTLA-4 in functionally defected Treg cells in MG and its actions involved in IVIg therapy.
American Psychological Association (APA)
Xu, Wenhua& Ren, Mingshan& Ghosh, Swagata& Qian, Kai& Luo, Zhaofeng& Zhang, Aimei…[et al.]. 2020. Defects of CTLA-4 Are Associated with Regulatory T Cells in Myasthenia Gravis Implicated by Intravenous Immunoglobulin Therapy. Mediators of Inflammation،Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1191687
Modern Language Association (MLA)
Xu, Wenhua…[et al.]. Defects of CTLA-4 Are Associated with Regulatory T Cells in Myasthenia Gravis Implicated by Intravenous Immunoglobulin Therapy. Mediators of Inflammation No. 2020 (2020), pp.1-13.
https://search.emarefa.net/detail/BIM-1191687
American Medical Association (AMA)
Xu, Wenhua& Ren, Mingshan& Ghosh, Swagata& Qian, Kai& Luo, Zhaofeng& Zhang, Aimei…[et al.]. Defects of CTLA-4 Are Associated with Regulatory T Cells in Myasthenia Gravis Implicated by Intravenous Immunoglobulin Therapy. Mediators of Inflammation. 2020. Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1191687
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1191687