Dynamic Changes of Innate Immune Cells in Pregnant Women With Autoimmune Thyroid Disease
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Frequency of Neutrophils in Peripheral Blood
研究概览
简要总结
Autoimmune thyroid disease (AITD) is the most common endocrine disorder in women of reproductive age, including during pregnancy. It encompasses two clinical conditions: autoimmune hyperthyroidism and hypothyroidism. Pregnancy significantly affects thyroid function regulation, while thyroid dysfunction can influence fertility, pregnancy progression, and the postpartum health. Although the role of acquired immunity in AITD is well understood, recent research increasingly emphasizes innate immunity. Key cells involved in innate immunity include neutrophils, monocytes, and NKT cells. However, limited data exist on their role during pregnancy, especially in women with AITD.
This study aims to investigate the dynamic changes in neutrophils, monocytes and NKT cells during pregnancy and compare findings between women with normal pregnancies and those with AITD.
The study will analyze the frequency and activation status of these innate immune cells in peripheral blood samples collected during the first, second, and third trimesters. In addition, concentrations of thyrotropin, thyroid hormones, thyroglobulin, and thyroid autoantibodies, will be measured. A thyroid ultrasound will also be performed.
详细描述
Autoimmune thyroid disease (AITD) affects approximately 2-17% of women of reproductive age, and represents the most common endocrine disorder in pregnancy. It includes autoimmune hyperthyroidism and hypothyroidism. Pregnancy has a significant impact on the regulation of thyroid function, and thyroid dysfunction may contribute to adverse pregnancy outcomes and neonatal complications.
Early detection of thyroid dysfunction during pregnancy is critical for optimal maternal-fetal health. While acquired immunity is a recognized contributor to the development of AITD, increasing attention has been given to the role of innate immunity. Innate immune mechanisms are essential for early immune response initiation and maintaining maternal tolerance toward the fetus, which represents a semi-allogeneic entity. This tolerogenic state is regulated both systemically and locally at the maternal-fetal interface.
The most relevant innate immune cells include neutrophils, monocytes/macrophages, and natural killer T (NKT) cells. Neutrophils participate in immune defense through cytotoxicity, phagocytosis, and cytokine secretion. Their numbers increase during pregnancy, and they play a role in implantation and placental development. Monocytes and decidual macrophages contribute to immune tolerance and placental remodeling. NKT cells, which bridge innate and adaptive immunity, perform immunoregulatory functions and have been observed in increased proportions in the decidua compared to peripheral blood. However, limited data are available regarding their role in pregnancy with thyroid autoimmunity.
The hypothesis of this study is that the numbers of neutrophils, monocytes and NKT cells and activation state of monocytes and NKT cells change during normal pregnancy and in pregnancy affected by AITD. The primary objective is to analyze differences in the frequency and activation marker expression of these immune cells between the two groups.
Peripheral blood mononuclear cells will be isolated, labeled, and analyzed using flow cytometry.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •adult healthy pregnant women and pregnant women with autoimmune thyroid disease
- •with a single pregnancy
- •older than 18 years
- •who have signed the informed consent form
排除标准
- •pregnant women who refuse to give informed consent
- •pregnant women under the age of 18
- •pregnant women with malignant diseases
- •pregnant women with thyrotoxicosis or hypothyroidism of a non-autoimmune nature and previous thyroidectomy or ablative therapy with iodine-131
- •pregnant women with an acute or chronic disease that is not an autoimmune thyroid disease
结局指标
主要结局
Frequency of Neutrophils in Peripheral Blood
时间窗: Within 24 months from enrollment; analysis over a 12-month period.
Frequency of neutrophils will be measured by differential blood count. Unit of Measure: Percent (%)
Frequency of Monocytes in Peripheral Blood
时间窗: Within 24 months from enrollment; analysis over a 12-month period.
Monocyte frequency will be measured by flow cytometry and expressed as percentage of monocytes among CD45⁺ leukocytes. Unit of Measure: Percent (%)
Frequency of NKT Cells in Peripheral Blood
时间窗: Within 24 months from enrollment; analysis over a 12-month period.
NKT cell frequency will be measured by flow cytometry and expressed as percentage of NKT cells within CD3⁺ T lymphocytes. Unit of Measure: Percent (%)
次要结局
- Expression of HLA-DR on Monocytes(Within 24 months from enrollment.)
- Serum Concentration of Free T3(Measured at each trimester; analysis completed within 12 months.)
- Serum Concentration of Thyroglobulin (Tg)(Measured at each trimester; analysis completed within 12 months.)
- Serum Concentration of TPOAb(Measured at each trimester; analysis completed within 12 months.)
- Expression of CD25 on NKT Cells(Within 24 months from enrollment.)
- Expression of CD69 on NKT Cells(Time Frame: Within 24 months from enrollment.)
- Serum Concentration of TSH(Measured at each trimester; analysis completed within 12 months of final collection.)
- Serum Concentration of TgAb(Measured at each trimester; analysis completed within 12 months.)
- Serum Concentration of antiTSHR(Measured at each trimester; analysis completed within 12 months.)
- Serum Concentration of Free T4(Measured at each trimester; analysis completed within 12 months.)
研究者
Tatjana Bogović Crnčić
Associate professor, MD, PhD, Head of the Department of Nuclear Medicine at Faculty of Medicine
University of Rijeka