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评价伴和不伴同种抗体的重型β地中海贫血患者调节性 T 细胞频率和 FoxP3/GDF-15 基因表达;与血清铁蛋白和叶酸水平的相关性。

Evaluation of regulatory T cells frequency and FoxP3/GDF-15 gene expression in β-thalassemia major patients with and without alloantibody; correlation with serum ferritin and folate levels.

机构信息

Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Ann Hematol. 2020 Mar;99(3):421-429. doi: 10.1007/s00277-020-03931-9. Epub 2020 Jan 27.

Abstract

β-thalassemia major is one of the most common hematologic disorders in the world. It causes severe anemia and patients require regular blood transfusions, which causes different complications such as iron overload and alloimmunization. Regulatory T cells (Tregs) have an important role in regulation of immune responses. FoxP3 is the major marker of Tregs and its expression can be influenced by different factors. GDF-15 is another gene that plays a role in iron homeostasis and regulation of immune system in different diseases. The aim of this study was to assess the frequency of Tregs and FoxP3/GDF-15 gene expression in β-thalassemia major patients with and without alloantibody as well as its correlation with different factors such as serum ferritin and folate levels. This study was conducted on 68 β-thalassemia major patients with and without alloantibodies in comparison with 20 healthy individuals with matched age and sex as control group. Enzyme-linked immunosorbent assay (ELISA), flow cytometry, and real-time PCR were performed in order to evaluate serum ferritin and folate levels, frequency of Tregs, and the expression of FoxP3 and GDF-15 genes, respectively. The percentage and absolute count of Tregs were increased in patients compared with controls (P = 0.0003), but there was no difference between responders and non-responders (P > 0.05). The Tregs count correlated positively with serum ferritin. No correlation was observed between target genes and serum ferritin and folate, but there was a positive significant correlation between the expression of FoxP3 and GDF-15 genes, which shows the immunosuppressive role of GDF-15.

摘要

β-地中海贫血是世界上最常见的血液系统疾病之一。它导致严重的贫血,患者需要定期输血,这会导致不同的并发症,如铁过载和同种免疫。调节性 T 细胞(Tregs)在免疫反应的调节中起着重要作用。FoxP3 是 Tregs 的主要标志物,其表达可以受到不同因素的影响。GDF-15 是另一种在不同疾病中发挥作用的基因,它在铁平衡和免疫系统调节中发挥作用。本研究旨在评估有无同种抗体的β-地中海贫血患者 Tregs 和 FoxP3/GDF-15 基因表达的频率,及其与血清铁蛋白和叶酸水平等不同因素的相关性。本研究共纳入 68 例有或无同种抗体的β-地中海贫血患者,并与 20 例年龄和性别相匹配的健康个体作为对照组。通过酶联免疫吸附试验(ELISA)、流式细胞术和实时 PCR 分别评估血清铁蛋白和叶酸水平、Tregs 频率以及 FoxP3 和 GDF-15 基因的表达。与对照组相比,患者的 Tregs 百分比和绝对计数增加(P = 0.0003),但应答者和无应答者之间无差异(P > 0.05)。Tregs 计数与血清铁蛋白呈正相关。目标基因与血清铁蛋白和叶酸之间无相关性,但 FoxP3 和 GDF-15 基因的表达呈正相关,这表明 GDF-15 具有免疫抑制作用。

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