ArticleRheumatology (Oxford, England)2017
CD3Z hypermethylation is associated with severe clinical manifestations in systemic lupus erythematosus and reduces CD3ζ-chain expression in T cells.
Article in Rheumatology (Oxford, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Systemic Lupus Erythematosus and DNA Degradation and Elimination Defects.Frontiers in immunology · 2019Pooled it
- Methylation of T and B Lymphocytes in Autoimmune Rheumatic Diseases.Clinical reviews in allergy & immunology · 2024Review
- Naturally Occurring Genetic Alterations in Proximal TCR Signaling and Implications for Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Glutaminase 1 Inhibition Reduces Glycolysis and Ameliorates Lupus-like Disease in MRL/lpr Mice and Experimental Autoimmune Encephalomyelitis.Arthritis & rheumatology (Hoboken, N.J.) · 2019Article
- Ankylosing spondylitis is associated with aberrant DNA methylation of IFN regulatory factor 8 gene promoter region.Clinical rheumatology · 2019Article
- Precision DNA demethylation ameliorates disease in lupus-prone mice.JCI insight · 2018Article
- Epigenetics of inflammatory arthritis.Current opinion in rheumatology · 2018Review
- DNA methylation 101: what is important to know about DNA methylation and its role in SLE risk and disease heterogeneity.Lupus science & medicine · 2018Article
- Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus.Frontiers in immunology · 2018Review
- Epigenetic involvement in etiopathogenesis and implications in treatment of systemic lupus erythematous.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Review
- SLE-Associated Defects Promote Altered T Cell Function.Critical reviews in immunology · 2017Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Objective: The importance of hypomethylation in SLE is well recognized; however, the significance of hypermethylation has not been well characterized. We screened hypermethylated marks in SLE and investigated their possible implications. Methods: DNA methylation marks were screened in SLE whole-blood DNA by microarray, and two marks ( CD3Z and VHL hypermethylations) were confirmed by a methylation single-base extension method in two independent ethnic cohorts consisting of 207 SLE patients and 151 controls. The correlation with clinical manifestations and the genetic influence on those epigenetic marks were analysed. Results: Two epigenetic marks, CD3Z and VHL hypermethylation, were significantly correlated with SLE: CD3Z hypermethylation (odds ratio = 7.76; P = 1.71 × 10 -13 ) and VHL hypermethylation (odds ratio = 3.77; P = 3.20 × 10 -8 ), and the increased CD3Z methylation was correlated with downregulation of the CD3ζ-chain in SLE T cells. In addition, less genetic influence on CD3Z methylation relative to VHL methylation was found in analyses of longitudinal and twin samples. Furthermore, a higher CD3Z methylation level was significantly correlated with a higher SLE disease activity index and more severe clinical manifestations, such as proteinuria, haemolytic anaemia and thrombocytopenia, whereas VHL hypermethylation was not. Conclusion: CD3Z hypermethylation is an SLE risk factor that can be modified by environmental factors and is associated with more severe SLE clinical manifestations, which are related to deranged T cell function by downregulating the CD3ζ-chain.
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Registered trials
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