TBX21是1型免疫反应的主要调节因子,在晚发性阿尔茨海默病患者外周血白细胞中过表达。

IF 5.2 2区 医学 Q1 GERIATRICS & GERONTOLOGY Immunity & Ageing Pub Date : 2023-11-10 DOI:10.1186/s12979-023-00385-1
S R Fatemi Langroudi, M Zeinaly, F Ajamian
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引用次数: 0

摘要

背景:外周免疫系统在神经退行性疾病病因中的作用最近得到了重视。全基因组关联研究(GWAS)最近发现了几个与阿尔茨海默病(AD)和抑郁症发展相关的候选免疫基因。驱动Th1免疫应答的TBX21(T-bet)与严重抑郁障碍(MDD)表型有关。本研究采用实时qPCR和Tetra ARMS PCR方法,研究了194名阿尔茨海默病患者和200名对照受试者的TBX21免疫基因与晚发性阿尔茨海默病(LOAD)发病率之间的关系。我们还使用了一种计算机方法来分析TBX21 rs17244587和rs41515744多态性在LOAD发病机制中的潜在影响。结果:LOAD患者外周血白细胞中TBX21“免疫基因”mRNA表达水平明显升高(P 结论:我们的研究结果首次表明了TBX21(T-bet)免疫基因在LOAD发展中的可能影响,并且LOAD患者WBCs中TBX21 mRNA的升高可能代表了阿尔茨海默病的一种新的简单诊断测试。
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TBX21, the Master regulator of the type 1 immune response, overexpresses in the leukocytes of peripheral blood in patients with late-onset Alzheimer's disease.

Background: The involvement of the peripheral immune system in the etiology of neurodegenerative diseases has recently been emphasized. Genome-wide association studies (GWAS) have recently identified several candidate immune genes linked to development of both Alzheimer's disease (AD) and depression. TBX21 (T-bet) which drives the Th1 immune response, is linked to the major depressive disorder (MDD) phenotype. This study investigated the association between the TBX21 immune gene and the possibility of late-onset Alzheimer's disease (LOAD) incidence in 194 LOAD and 200 control subjects using the real-time qPCR and the Tetra-ARMS-PCR methods. We also used an in silico approach to analyze the potential effects imparted by TBX21 rs17244587 and rs41515744 polymorphisms in LOAD pathogenesis.

Results: We found that the TBX21 "immune gene" had significantly elevated mRNA expression levels in the leukocytes of peripheral blood in patients with LOAD (P < 0.0001). We also found an upward trend in TBX21 expression with increasing age in LOAD patients compared to the control group (P < 0.05; CI = 95%). We noticed that the TT genotype of rs41515744 plays a protective role in LOAD incidence, as it attenuates the expression of TBX21 in the control group. We observed that the dominant model of rs41515744 represented a substantial association with LOAD (P = 0.019).

Conclusions: Our results show for the first time the likely impact of the TBX21 (T-bet) immune gene in LOAD development and that the elevated TBX21 mRNAs in the WBCs of LOAD patients may represent a new easy diagnostic test for Alzheimer's disease.

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来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
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