Table 1_Immunological reference intervals in pregnancy: longitudinal analysis of adaptive lymphocyte subsets.xlsx

BackgroundPregnancy induces profound immunological adaptations necessary to support fetal development while preserving maternal health. However, the systemic dynamics of less-studied adaptive immune cell subsets across gestation remain incompletely understood.
ObjectiveWe have conducted a comprehensive longitudinal analysis of peripheral B and T cell populations in healthy pregnant women in order to identify trimester-specific immune changes and to establish reference intervals for clinical and research use.
MethodsA total of 50 pregnant and 30 age-matched non-pregnant women were recruited in a prospective cohort study. Peripheral blood was collected at each trimester and analyzed by high-dimensional flow cytometry. We evaluated 74 lymphocyte subsets, including follicular and non-follicular CD4 and CD8 T cells, and functional markers CD69 and PD-L1, under basal and stimulated conditions.
ResultsPregnancy was associated with decreased total B cell counts, particularly within transitional and anergic naïve subsets, and increased activated naïve and memory B cells. T cell activation progressively increased in CD4 and CD8 subsets, especially during late pregnancy. Notably, activated circulating follicular helper T cells (cTfh) were consistently reduced throughout gestation compared to controls, while CD69 and PD-L1 expressions on CD4 and CD8 T cells increased in the third trimester. Maternal factors, including age, parity, miscarriage history, and BMI, significantly influenced specific immune profiles. Reference intervals were established for key subsets, and deviations in women who experienced pregnancy complications suggest potential predictive value for future risk assessment.
ConclusionsOur findings provide novel insights into the systemic immune adaptations that occur during pregnancy, particularly concerning follicular and non-follicular lymphocyte subsets. The proposed reference ranges proposed may serve as valuable tools for immunomonitoring and for identifying pregnancies at risk.

背景 妊娠可引发深刻的免疫学适应，这是支持胎儿发育同时维持母体健康所必需的。然而，目前对于妊娠全过程中研究较少的适应性免疫细胞亚群（adaptive immune cell subsets）的系统动力学特征，仍未得到充分阐明。
目的 本研究对健康妊娠女性的外周血B细胞与T细胞群开展了全面的纵向分析，旨在识别妊娠各分期特异性的免疫变化，并建立可供临床与科研使用的参考区间。
方法 本前瞻性队列研究共招募了50名妊娠女性与30名年龄匹配的非妊娠女性。在每个妊娠分期采集外周血样本，通过高维流式细胞术（high-dimensional flow cytometry）进行分析。本研究评估了74个淋巴细胞亚群，包括滤泡型与非滤泡型CD4及CD8 T细胞，以及基础状态与刺激状态下的功能标志物CD69与PD-L1（programmed death ligand 1）。
结果 妊娠与总B细胞计数降低相关，尤其体现在过渡型与无能初始淋巴细胞亚群中，同时活化初始与记忆性B细胞计数升高。CD4及CD8 T细胞亚群的活化程度随妊娠进展逐渐升高，尤其在妊娠晚期更为显著。值得注意的是，与对照组相比，活化的循环滤泡辅助性T细胞（cTfh）在整个妊娠过程中均持续减少；而CD4及CD8 T细胞上的CD69与PD-L1表达在妊娠晚期显著升高。母亲年龄、产次、流产史及身体质量指数（BMI）等母体因素可显著影响特定的免疫特征。本研究建立了关键细胞亚群的参考区间，而罹患妊娠并发症女性的免疫指标偏离情况提示其可为未来的风险评估提供潜在预测价值。
结论 本研究结果为妊娠期间发生的系统性免疫适应提供了新的见解，尤其聚焦于滤泡型与非滤泡型淋巴细胞亚群。本研究建立的参考区间可作为免疫监测以及识别高危妊娠的有效工具。