高龄孕妇妊娠早期蜕膜及外周血免疫状态变化的研究

Changes in immune status in decidua and peripheral blood during early pregnancy in women with advanced maternal age

摘要

目的 观察高龄妊娠女性早孕期母体免疫环境的变化。 方法 收集2024年1月至4月于重庆医科大学附属第三医院行早期人工流产的女性外周血及蜕膜组织，分为高龄组和对照组，其中高龄组蜕膜标本16例、外周血12例，对照组蜕膜标本23例、外周血13例。通过流式细胞术检测外周血淋巴细胞亚群：CD3⁺T细胞、CD4⁺T细胞、CD8⁺T细胞、CD19⁺B细胞、自然杀伤（natural killer，NK）细胞以及蜕膜NK（decidual NK，dNK）细胞亚群：dNK1（CD103^-CD18^-CD39⁺）、dNK2（CD103^- CD18⁺ CD39^-）、dNK3（CD103⁺ CD18⁺ CD39^-）。并采用化学发光免疫分析技术，检测外周血血清中的细胞因子。 结果 相较于对照组，高龄组外周血中CD3⁺T细胞、CD19⁺B细胞、NK细胞数量和百分比无明显差异，但高龄组CD4⁺T细胞占比［（40.25±6.40）%］较对照组［（35.29±3.95）%］增多（P=0.030），高龄组CD8⁺T细胞占比［（21.83±6.20）%］较对照组［（26.69±4.76）%］减少（P=0.041）；2组的dNK占总淋巴细胞的百分比无明显差异，dNK1及dNK2细胞亚群在蜕膜NK细胞中占比无明显差异，但高龄组的dNK3亚群占比［（45.21±11.40）%］相较于对照组［（22.93±6.93）%］明显增多（P<0.001）。高龄组血清细胞因子白细胞介素4（Interleukin-4，IL-4）水平低于对照组（P=0.017），同时干扰素γ（Interferon-γ，IFN-γ）水平也低于对照组（P=0.011），肿瘤坏死因子α（Tumor necrosis factor-α TNF-α）水平高于对照组（P=0.014）。 结论 高龄妊娠女性妊娠早期母体的免疫环境存在明显变化，dNK细胞亚群中dNK3细胞比例明显增高；外周血中存在CD4⁺T细胞比例增多和CD8⁺T细胞比例减少，IL-4和IFN-γ水平明显降低。

Abstract

Objective To investigate the changes in maternal immune environment during early pregnancy in women with advanced maternal age. Methods Peripheral blood and decidual tissue samples were collected from the women who underwent early induced abortion in The Third Affiliated Hospital of Chongqing Medical University from January to April 2024，and the women were divided into advanced age group（16 decidual tissue samples and 12 peripheral blood samples） and control group（23 decidual tissue samples and 13 peripheral blood samples）. Flow cytometry was used to measure peripheral blood lymphocyte subsets（CD3⁺T cells，CD4⁺T cells，CD8⁺T cells，CD19⁺ B cells，and natural killer［NK］ cells） and decidual NK（dNK） cell subsets including dNK1（CD103^- CD18^-CD39⁺），dNK2（CD103^-CD18⁺CD39^-），and dNK3 （CD103⁺ CD18⁺ CD39^-）. Chemiluminescent immunoassay was used to measure serum cytokines in peripheral blood. Results Compared with the control group，there was no significant difference in the number and percentage of CD3⁺ T cells，CD19⁺B cells，and NK cells in the peripheral blood of the senior group，but the percentage of CD4⁺ T cells in the senior group［（40.25±6.40）%］ was increased compared with that of the control group［（35.29±3.95）%］（P=0.030），and the percentage of CD8⁺T cells in the advance age group［（21.83±6.20）%］ was decreased（P=0.041） compared to the control group ［（26.69±4.76）%］. There was no significant difference between the two groups in the percentage of dNK in total lymphocytes and the percentages of dNK1 and dNK2 subsets in decidual NK cells，but the advanced age group［（45.21±11.40）%］ had a significantly higher percentage of dNK3 subset than the control group［（22.93±6.93）%］（P<0.001）. Compared with the control group in terms of serum cytokines，the advanced age group had significantly lower levels of interleukin-4（IL-4）（P=0.017） and interferon-γ（IFN-γ）（P=0.011）and a significantly higher level of tumor necrosis factor-α（P=0.014）. Conclusion There are significant changes in maternal immune environment during early pregnancy in women with advanced maternal age，with significant increases in the percentage of dNK3 cells in dNK cell subsets and the percentage of CD4⁺T cells in peripheral blood and significant reductions in the percentage of CD8⁺T cells and the levels of IL-4 and IFN-γ in the peripheral blood.

关键词

高龄妊娠 / 母胎界面 / 免疫调节 / 淋巴细胞亚群 / 蜕膜NK细胞 / 细胞因子

Key words

advanced maternal age / maternal-fetal interface / immune regulation / lymphocyte subsets / decidual natural killer cells / cytokines

基金资助

罗元恺滋肾育胎丸中青年科研基金资助项目(20190812)