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妊娠期糖尿病与针对 的特异性体液和细胞免疫应答的负调节有关。

Association of gestational diabetes mellitus and negative modulation of the specific humoral and cellular immune response against .

机构信息

Laboratory of Immunology, Institute of Biological and Natural Sciences, Department of Microbiology, Immunology and Parasitology, Universidade Federal do Triângulo Mineiro (UFTM), Uberaba, Minas Gerais, Brazil.

Laboratory of Cellular Interactions, Institute of Biological and Natural Sciences, Department of Structural Biology, Universidade Federal do Triângulo Mineiro (UFTM), Uberaba, Minas Gerais, Brazil.

出版信息

Front Immunol. 2022 Sep 20;13:925762. doi: 10.3389/fimmu.2022.925762. eCollection 2022.

DOI:10.3389/fimmu.2022.925762
PMID:36203592
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9531261/
Abstract

In order to evaluate and compare the specific immune response of pregnant women (PW) chronically infected with , with and without gestational diabetes mellitus (GDM), and the humoral response of their respective newborns (NB), the study was carried out on 81 PW (34 GDM and 47 controls) from whose medical records the results of the oral glucose tolerance test (OGTT) were obtained, and blood samples were collected at the third trimester of pregnancy; also, on 45 NBs (20 GDM and 25 controls) from whom umbilical cord blood samples were obtained. Humoral immunity was analyzed by measuring anti- total IgG, IgG subclasses and IgG avidity. To evaluate cellular immunity, peripheral blood mononuclear cells (PBMC) from 32 PW (16 GDM and 16 controls) were cultured, supernatant cytokines were determined, and flow cytometry was performed to analyze the expression at lymphocytes of surface molecules, cytokines and transcription factors. All PW and NBs were positive for total IgG, and the prevalent subclass was IgG1. There was a negative correlation between the OGTT glycemia of PW and the levels of total IgG, IgG1 and IgG avidity. The IgG avidity of the GDM group was significantly lower than the control group. Patients from the GDM group had a higher number of T lymphocytes expressing markers of cell activation and exhaustion (CD28 and PD-1). In the presence of soluble antigen (STAg) the amount of CD4 T cells producing IFN-γ, IL-10 and IL-17 was significantly lower in the GDM group, while there was no difference between groups in the number of CD4 CD25FOXP+LAP+ functional Treg cells. Additionally, under STAg stimulus, the secretion of IL-17, IL-4, TNF and IL-2 cytokines at PBMCs culture supernatant was lower in the GDM group. In conclusion, there was a correlation between the increase in blood glucose and the decrease in levels of anti- antibodies, associated with the decreased IgG avidity in patients who develop GDM. Also, the GDM group had decreased immune responses in Th1, Th2 and Th17 profiles, suggesting an association between GDM and the negative modulation of the humoral and cellular immune responses against .

摘要

为了评估和比较慢性感染 的孕妇(PW)与妊娠合并糖尿病(GDM)和无妊娠合并糖尿病孕妇(PW)的特异性免疫反应,以及其新生儿(NB)的体液免疫反应,本研究对 81 名 PW(34 名 GDM 和 47 名对照)进行了研究,从这些 PW 的病历中获得了口服葡萄糖耐量试验(OGTT)的结果,并在妊娠晚期采集了血液样本;还从 45 名 NB(20 名 GDM 和 25 名对照)中采集了脐血样本。通过测量抗总 IgG、IgG 亚类和 IgG 亲和力来分析体液免疫。为了评估细胞免疫,从 32 名 PW(16 名 GDM 和 16 名对照)中培养外周血单核细胞(PBMC),测定上清液细胞因子,并通过流式细胞术分析淋巴细胞表面分子、细胞因子和转录因子的表达。所有 PW 和 NB 均为总 IgG 阳性,流行的亚类为 IgG1。PW 的 OGTT 血糖与总 IgG、IgG1 和 IgG 亲和力水平呈负相关。GDM 组的 IgG 亲和力明显低于对照组。GDM 组患者表达细胞活化和耗竭标志物(CD28 和 PD-1)的 T 淋巴细胞数量较多。在可溶性抗原(STAg)存在的情况下,GDM 组 CD4 T 细胞产生 IFN-γ、IL-10 和 IL-17 的数量明显减少,而两组 CD4 CD25FOXP+LAP+功能性 Treg 细胞数量无差异。此外,在 STAg 刺激下,GDM 组 PBMC 培养上清液中 IL-17、IL-4、TNF 和 IL-2 细胞因子的分泌量较低。总之,血糖升高与抗抗体水平降低相关,与发生 GDM 的患者 IgG 亲和力降低相关。此外,GDM 组 Th1、Th2 和 Th17 表型的免疫反应降低,提示 GDM 与针对 的体液和细胞免疫反应的负调节有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a23/9531261/5d7af60490d7/fimmu-13-925762-g008.jpg
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