Ghavidel Afshin Abdi, Farivar Shirin, Aghamiri Shahin, Shiari Reza
Pediatric Infectious Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University GC, Tehran, Iran.
Reumatologia. 2022;60(1):26-34. doi: 10.5114/reum.2022.114228. Epub 2022 Feb 28.
Juvenile idiopathic arthritis (JIA) is a childhood autoimmune rheumatoid disease. Past studies have confirmed that JIA is a complex disease, which means that genes and environmental factors affect the aetiology of the disease. In this study, we analysed the expression of interleukin 32, forkhead box P3 (FOXP3), methyl-CpG binding domain protein 1 (MBD1), and methyl-CpG-binding protein 2 (MECP2) in peripheral blood mononuclear cells of children with JIA in comparison with the expression of those in healthy children. Interleukin 32 is an inflammatory factor, FOXP3 is a transcription factor, and MBD1 and MECP2 are binding proteins that bind to the methylated deoxyribonucleic acid (DNA).
We collected blood from JIA patients who had been diagnosed and classified into clinical subtypes by a rheumatologist from the division of paediatric rheumatology. Healthy children, whose clinical and preclinical analysis confirmed they had no disease and just came to the hospital for a check-up or minor surgical procedures were considered as a control group. Age and gender were matched in patients and the control group. Total ribonucleic acid was extracted from blood, and cDNA was synthesized. Eventually, the transcript levels were analysed by quantitative polymerase chain reaction, and statistical analysis was carried out.
Statistical analysis of gene expressions in young females affected by JIA demonstrated that MECP2 and FOXP3 were increased significantly (-value = 0.002 and 0.05, respectively). Interleukin 32 gene expression was also increased (-value = 0.14), whereas MBD1 gene expression was decreased (-value = 0.06); however, these changes in the expression of all 4 genes were not significant in young males.
Different expression levels of the mentioned genes between affected young females and males result from hormones in both gender and also methotrexate (MTX) drug. Also, the reason affected young females are more prone to JIA than males can be the lower level of FOXP3 expression in healthy females than healthy males.
幼年特发性关节炎（JIA）是一种儿童自身免疫性类风湿疾病。既往研究证实JIA是一种复杂疾病，这意味着基因和环境因素会影响该疾病的病因。在本研究中，我们分析了JIA患儿外周血单个核细胞中白细胞介素32、叉头框蛋白P3（FOXP3）、甲基化CpG结合域蛋白1（MBD1）和甲基化CpG结合蛋白2（MECP2）的表达，并与健康儿童中这些蛋白的表达进行比较。白细胞介素32是一种炎症因子，FOXP3是一种转录因子，MBD1和MECP2是与甲基化脱氧核糖核酸（DNA）结合的结合蛋白。
我们从由儿科风湿病科的风湿病学家诊断并分类为临床亚型的JIA患者中采集血液。临床和临床前分析证实无疾病且仅因体检或小手术前来医院的健康儿童被视为对照组。患者和对照组在年龄和性别上相匹配。从血液中提取总核糖核酸，并合成互补DNA（cDNA）。最终，通过定量聚合酶链反应分析转录水平，并进行统计分析。
对受JIA影响的年轻女性的基因表达进行统计分析表明，MECP2和FOXP3显著增加（P值分别为0.002和0.05）。白细胞介素32基因表达也增加（P值为0.14），而MBD1基因表达降低（P值为0.06）；然而，所有这4种基因表达的这些变化在年轻男性中并不显著。
受影响的年轻女性和男性之间上述基因的表达水平不同是由两性中的激素以及甲氨蝶呤（MTX）药物导致的。此外，受影响的年轻女性比男性更容易患JIA的原因可能是健康女性中FOXP3的表达水平低于健康男性。
