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糖尿病妊娠中的胸腺生长与胎儿免疫反应

Thymus Growth and Fetal Immune Responses in Diabetic Pregnancies.

作者信息

Warncke Katharina, Lickert Ramona, Eitel Stephanie, Gloning Karl-Philipp, Bonifacio Ezio, Sedlmeier Eva-Maria, Becker Petra, Knoop Jan, Beyerlein Andreas, Ziegler Anette-Gabriele

机构信息

Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany.

Forschergruppe Diabetes e.V., Neuherberg, Germany.

出版信息

Horm Metab Res. 2017 Nov;49(11):892-898. doi: 10.1055/s-0043-120671. Epub 2017 Nov 14.

DOI:10.1055/s-0043-120671
PMID:29136677
Abstract

Type 1 diabetes (T1D) during pregnancy possibly affects the development of the thymus and the maturation of the immune system in the offspring. The aim of the ImmunDiabRisk study was to investigate thymus growth and maternal and fetal immune responses in pregnancies with and without T1D. The thymus circumferences of the fetuses of pregnant women with T1D (n=49) and without diabetes (n=59) were measured using ultrasound around the 29th gestational week and standardized for gestational age. Simultaneously, the frequencies and total numbers of cell markers were analyzed by flow cytometry in maternal peripheral blood, and at birth in umbilical cord blood. The standardized circumference of the thymus was similar in fetuses of mothers with and without T1D (p=0.26). We observed higher numbers of FOXP3 Tregs, memory Tregs, erythrocytes, and lymphocytes in the cord blood from T1D pregnancies (p=0.01, p=0.002, p=0.002 and p=0.02, respectively). The frequencies of CD4+/CD8+ T cells correlated positively in maternal blood and umbilical cord blood of mother-child pairs, as did the levels of neutrophils (Spearman's correlation coefficient r=0.43, p=0.02 for CD4+/CD8+ cells; r=0.46, p=0.03 for neutrophils), while no significant correlations were observed between thymus circumference and any cell markers in the child. Parts of the prenatal immune system seem to develop differently in the offspring of mothers with and without T1D. The correlation of Tregs between maternal blood and cord blood may indicate a significant cross-talk between the maternal and fetal immune system.

摘要

孕期1型糖尿病(T1D)可能会影响后代胸腺的发育及免疫系统的成熟。ImmunDiabRisk研究的目的是调查患T1D和未患T1D的孕妇孕期中胸腺的生长情况以及母婴的免疫反应。在孕29周左右,采用超声测量了49例患T1D孕妇和59例未患糖尿病孕妇胎儿的胸腺周长,并根据孕周进行了标准化处理。同时,通过流式细胞术分析了孕妇外周血及出生时脐带血中细胞标志物的频率和总数。患T1D和未患T1D孕妇胎儿的胸腺标准化周长相似(p = 0.26)。我们观察到,T1D妊娠的脐带血中FOXP3调节性T细胞(Tregs)、记忆性Tregs、红细胞和淋巴细胞数量较多(分别为p = 0.01、p = 0.002、p = 0.002和p = 0.02)。母婴对中母体血液和脐带血中CD4⁺/CD8⁺ T细胞的频率呈正相关,中性粒细胞水平也是如此(Spearman相关系数r = 0.43,CD4⁺/CD8⁺细胞p = 0.02;r = 0.46,中性粒细胞p = 0.03),而在儿童中,胸腺周长与任何细胞标志物之间均未观察到显著相关性。产前免疫系统的某些部分在患T1D和未患T1D母亲的后代中似乎发育不同。母体血液和脐带血中Tregs的相关性可能表明母婴免疫系统之间存在显著的相互作用。

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