Description of human AAA by cytokine and immune cell aberrations compared to risk-factor matched controls.

Description of human AAA by cytokine and immune cell aberrations compared to risk-factor matched controls.
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DOI:
10.1016/j.surg.2018.03.002
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发表时间:
2018-08
期刊:
影响因子:
3.8
通讯作者:
Murphy MP
Murphy MP
中科院分区:
医学2区
文献类型:
--
作者:
Wang SK;Green LA;Gutwein AR;Drucker NA;Motaganahalli RL;Gupta AK;Fajardo A;Murphy MP

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导致腹主动脉瘤(AAA)形成的发病机制仍然知之甚少。因此,我们系统地定义了与风险因子匹配(RFM)对照相比,在人AAA中观察到的细胞因子和循环免疫细胞环境。从2015年到2017年,有274名患者向印第安纳州大学主动脉疾病中心(IUCAD)献血。使用酶联免疫吸附测定法(ELISA)测定循环细胞因子的绝对浓度,同时通过流式细胞术分析测定循环免疫细胞表型的表达。人AAA的特征在于抗原特异性、CD 4 + Tr 1调节性淋巴细胞的显著耗竭,这对应于抗原特异性、炎性Th 17细胞的上调。Treg、B10和髓源性抑制(MDSC)调节细胞的发生率无差异。同样,在以下炎性细胞因子中未观察到差异:IL-1β、C反应蛋白(CRP)、肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)和IL-23。然而,观察到炎性细胞因子骨桥蛋白(OPN)、IL-6和IL-17的显著上调。此外,在调节细胞因子IL-2、IL-4、IL-13、TNF刺激基因6蛋白(TSG-6)和前列腺素E2(PGE 2)中未观察到变化,但我们确实观察到必需调节细胞因子IL-10显著降低。在这项研究中,我们系统地描述了AAA的免疫环境,并提出了初步证据,错误的免疫调节也可能有助于动脉瘤的形成和生长。
The pathogenesis driving the formation of abdominal aortic aneurysms (AAA) continues to be poorly understood. Therefore, we systemically define the cytokine and circulating immune cell environment observed in human AAA compared to risk-factor matched (RFM) controls. From 2015 to 2017, 274 patients donated blood to the Indiana University Center for Aortic Disease (IUCAD). Absolute concentrations of circulating cytokines were determined using enzyme-linked immunosorbent assays (ELISA) while expression of circulating immune cell phenotypes were assayed via flow cytometric analysis. Human AAA is characterized by a significant depletion of the antigen-specific, CD4+ Tr1 regulatory lymphocyte which corresponds to an upregulation of the antigen-specific, inflammatory Th17 cell. There were no differences in the incidence of Treg, B10, and myeloid-derived suppressor (MDSC) regulatory cells. Similarly, no disparities were noted in the following inflammatory cytokines: IL-1β, C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), and IL-23. However, significant upregulation of the inflammatory cytokines osteopontin (OPN), IL-6, and IL-17 were noted. Additionally, no changes were observed in the regulatory cytokines IL-2, IL-4, IL-13, TNF-stimulated gene 6 protein (TSG-6), and prostaglandin E2 (PGE2), but we did observe a significant decrease in the essential regulatory cytokine IL-10. In this investigation, we systematically characterize the AAA immune environment and present preliminary evidence that faulty immune regulation may also contribute to aneurysm formation and growth.
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