CTLA-4 methylation regulates the pathogenesis of myasthenia gravis and the expression of related cytokines.
|Abstract||Myasthenia gravis (MG) is a progressive autoimmune disease that occurs as a result of the failure of neuromuscular transmission and is characterized by muscle weakness. There has been evidence on the correlations between the genetic predisposition of cytotoxic T lymphocyte and the antigen-4 (CTLA-4) and MG. Thus, the present study was conducted to study is designed to examine the effects of CTLA-4 methylation on the pathogenesis of MG and the expressions of related cytokines.|
Mucosal tolerance to experimental autoimmune myasthenia gravis is associated with down-regulation of AChR-specific IFN-gamma-expressing Th1-like cells and up-regulation of TGF-beta mRNA in mononuclear cells.
|Publication Year Start||2018-01-01|
PMID- 29718870 OWN - NLM STAT- MEDLINE DCOM- 20180508 LR - 20180508 IS - 1536-5964 (Electronic) IS - 0025-7974 (Linking) VI - 97 IP - 18 DP - 2018 May TI - CTLA-4 methylation regulates the pathogenesis of myasthenia gravis and the expression of related cytokines. PG - e0620 LID - 10.1097/MD.0000000000010620 [doi] AB - BACKGROUND: Myasthenia gravis (MG) is a progressive autoimmune disease that occurs as a result of the failure of neuromuscular transmission and is characterized by muscle weakness. There has been evidence on the correlations between the genetic predisposition of cytotoxic T lymphocyte and the antigen-4 (CTLA-4) and MG. Thus, the present study was conducted to study is designed to examine the effects of CTLA-4 methylation on the pathogenesis of MG and the expressions of related cytokines. METHODS: The CTLA-4 methylation levels in peripheral blood were quantified in 103 samples collected from MG patients and 86 samples from healthy individiuals. The expression of serum-related cytokines as well as the Treg cell ratio were examined so as to define the contributory role of CTLA-4 methylation in MG and to identify the interaction between CTLA-4 methylation and related factors, the expressions of DNA methyltransferase (DNMT)l, DNMT3A and DNMT3B, CTLA-4, AchR-Ab, Titin-Ab, RyR-Ab, IL-2, IL-10, IFN-gamma, and TGF-beta, activity of P- acetylcholinesterase (AchE) and E-AchE. RESULTS: The results indicated that the incidence of CTLA-4 methylation was significantly higher in the control group when compared with the MG group, and CTLA-4 methylation was also found to be associated with the thymus status of MG patients. It was also observed from the experiment data that the expressions of DNMTl, DNMT3A, and DNMT3B, along with the expressions of AchR-Ab, Titin-Ab, RyR-Ab, IL-2, IL-10, IFN-gamma and TGF-beta, and the activity of P-AchE and E-AchE were all higher in the MG group than in the control group, with a reduction of CTLA-4 expression. Another key finding from this study revealed that methylation interference can lead to the suppression in the expression of AchR-Ab, the activity of E-AchE, the expression of IL-2, IL-10, IFN-gamma, and TGF-beta and the Treg cell ratio in lymphocytes. CONCLUSION: In conclusion, the results obtained from the present study highly indicated that CTLA-4 methylation might play a role in facilitating the occurrence of MG and increasing the expressions of related cytokines through the upregulation of AchR-Ab and E-Ach. FAU - Fang, Ti-Kun AU - Fang TK AD - Department of Emergency, Jining No.1 People's Hospital, Jining, Shandong Province, P.R. China. FAU - Yan, Cheng-Jun AU - Yan CJ FAU - Du, Juan AU - Du J LA - eng PT - Journal Article PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (CTLA-4 Antigen) RN - 0 (CTLA4 protein, human) RN - 0 (Cytokines) RN - EC 18.104.22.168 (Acetylcholinesterase) SB - AIM SB - IM MH - Acetylcholinesterase/blood MH - Adolescent MH - Adult MH - Aged MH - Animals MH - CTLA-4 Antigen/*blood MH - Child MH - Cytokines/*blood MH - Disease Models, Animal MH - Female MH - Humans MH - Male MH - Methylation MH - Middle Aged MH - Myasthenia Gravis/*blood/pathology MH - Rats, Inbred Lew MH - T-Lymphocytes, Regulatory/metabolism MH - Up-Regulation MH - Young Adult EDAT- 2018/05/03 06:00 MHDA- 2018/05/09 06:00 CRDT- 2018/05/03 06:00 PHST- 2018/05/03 06:00 [entrez] PHST- 2018/05/03 06:00 [pubmed] PHST- 2018/05/09 06:00 [medline] AID - 10.1097/MD.0000000000010620 [doi] AID - 00005792-201805040-00038 [pii] PST - ppublish SO - Medicine (Baltimore). 2018 May;97(18):e0620. doi: 10.1097/MD.0000000000010620.