Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; National Public Health Laboratory, Khartoum.
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran.
Reumatismo. 2020 Jul 23;72(2):93-102. doi: 10.4081/reumatismo.2020.1235.
Rheumatoid arthritis (RA), a form of inflammatory arthritis, is a chronic joint disease characterized by pain and inflammation that affects 0.5% to 1% of the population worldwide. The safety, efficacy, tolerability, and potency of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property has been reported by several in vitro studies, experimental models and clinical trials phase I/II and III in ankylosing spondylitis and rheumatoid arthritis (RA) patients This research is designed to study the therapeutic efficacy of oral administration of mannuronic acid in RA patients who had inadequate response to conventional drugs and to assess the effect of this drug on gene expression of the signal transducer and activator of transcription (STATs) protein (STAT1, STAT3, STAT4, and STAT6). The study has included 15 RA patients who had an insufficient response to the conventional therapy. The oral dose of mannuronic acid was 1000mg divided into two 500 mg doses per day for 3 months as an addition to conventional therapy. There were 15 healthy volunteer in the control group. Blood samples were collected from both groups, once from healthy controls and twice from RA patients before and after treatment by M2000. The peripheral blood mononuclear cells (PBMCs) were isolated to assess the gene expression level of STAT1, STAT3, STAT4, and STAT6 using the real-time PCR method. Results obtained in this study demonstrated a significant difference in the gene expression level of STAT1 between healthy controls and patients before treatment as well as a significant reduction in RA patients after treatment compared with the level before treatment. In addition, the gene expression level of STAT3 and STAT4 showed a significant reduction in RA patients after treatment compared to patients before treatment, while there was no significant difference between RA patients before treatment and the healthy control group for both molecules. On the other hand, there was no change in the gene expression level of STAT6 among all groups. The outcomes of this study confirmed that β-D-mannuronic acid (M2000) has the ability to control the levels of STAT1, STAT3 and STAT4 in RA patients, and might be beneficial in the management and therapy of RA.
类风湿性关节炎（RA）是一种炎症性关节炎，是一种慢性关节疾病，以疼痛和炎症为特征，影响全球 0.5%至 1%的人口。β-D-甘露糖醛酸（M2000）作为一种具有免疫抑制特性的新型非甾体抗炎药，其安全性、有效性、耐受性和效力已在几项体外研究、实验模型和临床试验 I/II 期和 III 期中得到证实，适用于强直性脊柱炎和类风湿性关节炎（RA）患者。本研究旨在研究口服甘露糖醛酸治疗对常规药物治疗反应不足的 RA 患者的治疗效果，并评估该药物对信号转导和转录激活因子（STATs）蛋白（STAT1、STAT3、STAT4 和 STAT6）基因表达的影响。该研究纳入了 15 名对常规治疗反应不足的 RA 患者。口服甘露糖醛酸剂量为 1000mg，分为每天两次，每次 500mg，共 3 个月，作为常规治疗的补充。对照组包括 15 名健康志愿者。从两组中采集血样，健康对照组采集一次，RA 患者在治疗前和治疗后两次采集，通过 M2000 采集。分离外周血单核细胞（PBMCs），采用实时 PCR 法评估 STAT1、STAT3、STAT4 和 STAT6 的基因表达水平。本研究结果表明，健康对照组和治疗前 RA 患者的 STAT1 基因表达水平存在显著差异，治疗后 RA 患者的 STAT1 基因表达水平明显低于治疗前。此外，治疗后 RA 患者的 STAT3 和 STAT4 基因表达水平明显低于治疗前，而这两种分子在治疗前 RA 患者与健康对照组之间无显著差异。另一方面，各组之间 STAT6 的基因表达水平没有变化。本研究结果证实，β-D-甘露糖醛酸（M2000）能够控制 RA 患者 STAT1、STAT3 和 STAT4 的水平，可能有益于 RA 的管理和治疗。
