The status of FOXP3 gene methylation in pediatric systemic lupus erythematosus.,Allergologia et Immunopathologia

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The status of FOXP3 gene methylation in pediatric systemic lupus erythematosus.
Allergologia et Immunopathologia ( IF 2.5 ) Pub Date : 2020-05-29 , DOI: 10.1016/j.aller.2020.03.014
S Hanaei ₁ , G Sanati ₂ , S Zoghi ₃ , S Gharibzadeh ₄ , V Ziaee ₅ , N Rezaei ₆

Affiliation

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Molecular Immunology Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Vienna, Austria; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran.
Division of Pediatric Rheumatology, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Stockholm, Sweden.

Background

Systemic lupus erythematosus (SLE) is an autoimmune disease caused by interaction of genetic, epigenetic, and environmental factors. One of the important epigenetic factors in SLE would be methylation of immune-related genes, such as FOXP3, which plays a role in activating the regulation and also the function of T cells. To date, the relationship between levels of serum bio-markers and the susceptibility to lupus in children has not been well-understood. In this study, the involvement of etiologic factors, such as methylation of FOXP3 gene, was investigated in children with SLE.

Method

Twenty-four female children with SLE and 25 female healthy subjects without any history of autoimmune and inflammatory diseases were included in this study. Blood samples were obtained and DNA was extracted from the blood cells. The bisulphite method was used to convert the DNA using the MethylEdge™ Bisulfite Conversion System Kit. Then, methylation of the gene was investigated using Real Time methylation specific PCR.

Results

The FOXP3 DNA methylation in patients and healthy subjects was significantly different. While the median unmethylated DNA in patients was 0.57 ± 0.43, it was 0.97 ± 0.83 in healthy subjects (P = 0.012). The Demethylation Index in patients was 0.007 ± 0.003, significantly lower than in controls (0.014 ± 0.013; P = 0.012).

Conclusions

The FOXP3 gene methylation in children with SLE was significantly higher than healthy subjects, which could possibly affect the level of gene expression. Therefore, one of the causes of increased immune response in SLE can be the lower expression of FOXP3 by hypermethylation of this gene.

中文翻译：

FOXP3基因甲基化在小儿系统性红斑狼疮中的地位。

背景

系统性红斑狼疮（SLE）是一种遗传性，表观遗传性和环境因素相互作用引起的自身免疫性疾病。SLE中重要的表观遗传因素之一是免疫相关基因（如FOXP3）的甲基化，该基因在激活T细胞的调节以及功能中起着重要作用。迄今为止，对儿童血清生物标志物水平与对狼疮的易感性之间的关系尚未得到很好的理解。在这项研究中，对SLE儿童的病因进行了研究，例如FOXP3基因的甲基化。