Radboud Institute for Molecular Life Sciences, Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands.
Radboud Institute for Molecular Life Sciences, Department of Laboratory Medicine, Laboratory of Medical Immunology, Section Pediatric Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
Front Immunol. 2021 Oct 28;12:735564. doi: 10.3389/fimmu.2021.735564. eCollection 2021.
Pregnancy after renal transplantation is associated with an increased risk of complications. While a delicately balanced uterine immune system is essential for a successful pregnancy, little is known about the uterine immune environment of pregnant kidney transplant recipients. Moreover, children born to kidney transplant recipients are exposed to immunosuppressive drugs, with possible consequences for neonatal outcomes. Here, we defined the effects of kidney transplantation on the immune cell composition during pregnancy with a cohort of kidney transplant recipients as well as healthy controls with uncomplicated pregnancies. Maternal immune cells from peripheral blood were collected during pregnancy as well as from decidua and cord blood obtained after delivery. Multiparameter flow cytometry was used to identify and characterize populations of cells. While systemic immune cell frequencies were altered in kidney transplant patients, immune cell dynamics over the course of pregnancy were largely similar to healthy women. In the decidua of women with a kidney transplant, we observed a decreased frequency of HLA-DR Treg, particularly in those treated with tacrolimus versus those that were treated with azathioprine next to tacrolimus, or with azathioprine alone. In addition, both the innate and adaptive neonatal immune system of children born to kidney transplant recipients was significantly altered compared to neonates born from uncomplicated pregnancies. Overall, our findings indicate a significant and distinct impact on the maternal systemic, uterine, and neonatal immune cell composition in pregnant kidney transplant recipients, which could have important consequences for the incidence of pregnancy complications, treatment decisions, and the offspring's health.
肾移植后妊娠与并发症风险增加相关。虽然子宫内微妙平衡的免疫系统对成功妊娠至关重要，但对于妊娠肾移植受者的子宫免疫环境知之甚少。此外，肾移植受者所生的儿童暴露于免疫抑制剂下，可能对新生儿结局产生影响。在这里，我们通过肾移植受者队列以及无并发症妊娠的健康对照者，定义了肾移植对妊娠期间免疫细胞组成的影响。在妊娠期间以及分娩后从蜕膜和脐带血中采集母体外周血免疫细胞。多参数流式细胞术用于鉴定和描述细胞群。虽然肾移植患者的全身免疫细胞频率发生改变，但妊娠过程中的免疫细胞动态在很大程度上与健康女性相似。在肾移植女性的蜕膜中，我们观察到 HLA-DR Treg 的频率降低，尤其是在接受他克莫司治疗的患者中，与接受他克莫司加硫唑嘌呤或单独接受硫唑嘌呤治疗的患者相比。此外，与无并发症妊娠所生的新生儿相比，肾移植受者所生儿童的固有和适应性新生儿免疫系统均发生显著改变。总体而言，我们的研究结果表明，妊娠肾移植受者的母体全身、子宫和新生儿免疫细胞组成受到显著而独特的影响，这可能对妊娠并发症的发生率、治疗决策以及后代的健康产生重要影响。
