Investigation of the maternal immune phenotype in women with recurrent pregnancy loss due to chronic histiocytic intervillositis

研究的主要主题：我的项目旨在发现一种罕见但毁灭性的怀孕疾病的原因，这种疾病会导致反复流产和死胎。慢性组织细胞间绒毛炎（CHI）的发生率为万分之一，但其复发风险非常高，这意味着一些受影响的夫妇已经经历了几次流产。只有大约一半的CHI妊娠婴儿存活下来，其中一半以上将非常早产，对他们的健康造成长期影响。父母承受这些反复失去亲人的情感负担是巨大的。我们选择研究这种疾病是希望改善受影响家庭的前景。CHI的病因尚不清楚，只能在怀孕结束后通过显微镜下分析胎盘来诊断。在随后的怀孕中，除了在超声波扫描中识别出一个非常小的婴儿外，没有证明复发的警告信号，也没有可靠的测试可以预测怀孕是成功还是失败。也没有任何治疗方法可以持续防止CHI复发。该项目的主要目标是：目前的科学证据表明，CHI是由母亲在怀孕期间攻击胎盘的抗体引起的。这会阻止胎盘发育，阻止未出生的婴儿正常生长。我们的目标是鉴定这种抗体，以提高我们对CHI病因的了解。我还将研究患有CHI的妇女子宫内膜的免疫细胞，以进一步发现导致复发性流产的原因。确定CHI的病因对发现预防复发的治疗方法至关重要，并为受影响的妇女提供健康婴儿的希望。研究的结构和设置：研究将分为两个部分：首先，寻找一种攻击CHI胎盘的母源抗体；其次，对CHI女性子宫内膜（子宫内膜）免疫细胞功能的研究。第一部分将在伦敦大学学院妇女健康研究所进行，这是一个充满活力的医生和科学家社区，致力于改善妇女健康的各个方面。该研究所主持了几项高知名度的相关研究，调查了严重的胎儿生长限制等问题，并在将创新的母婴新疗法引入临床试验方面有着良好的记录。因此，它代表了这项研究的完美环境。第二个部分将在瑞典进行，这要归功于与斯德哥尔摩卡罗林斯卡研究所的科学家们令人兴奋的合作。这将使我们能够学习和实施开创性的新技术，用于研究子宫内膜免疫细胞及其在胎盘健康和疾病中的作用。这些细胞以前从未在CHI女性中进行过研究，我们的发现可能在理解为什么这些女性和其他人会复发性流产方面发挥关键作用。潜在影响：本研究旨在造福患者。发现CHI的原因将使我们更接近能够设计和实施新的治疗方法，以防止复发性流产。我们希望我们的发现可以成为未来CHI临床试验的基础，并且它们也可能为不明原因的复发性妊娠丢失的研究提供有用的模型。我们的发现也可以帮助医生和科学家解决其他由抗体引起的疾病，比如狼疮。我们致力于从受影响的患者和家属那里了解他们的研究重点，他们对围产期丧亲护理的看法，以及他们与一种鲜为人知的导致反复流产的疾病生活的独特经历。我们希望提高这种被忽视疾病的知名度，以刺激进一步的研究，并在未来改善患者的预后。

Principal subject of the research: My project aims to discover the cause of a rare but devastating disease of pregnancy that causes repeated miscarriage and stillbirth. Chronic histiocytic intervillositis (CHI) affects 1 in 10,000 pregnancies but carries a very high risk of recurrence, meaning that some affected couples have suffered several pregnancy losses. Only about half of all babies in CHI pregnancies survive, and over half of these will be born very premature, causing long-term consequences for their health. The emotional burden for parents enduring these repeated losses is immense. We have chosen to study this disease in the hope of improving the outlook for affected families.The cause of CHI is unknown and it can only be diagnosed after a pregnancy has ended, by analysing the placenta under a microscope. In a subsequent pregnancy, apart from recognising a very small baby on ultrasound scans, there are no proven warning signs of recurrence and no reliable test that can predict whether the pregnancy will succeed or fail. There is also no treatment that can consistently prevent CHI from recurring. The project's key aims:Current scientific evidence suggests that CHI is caused by an antibody from the mother that attacks the placenta during pregnancy. This prevents the placenta from developing and stops the unborn baby from growing normally. We aim to identify this antibody in order to improve our understanding of the cause of CHI. I will also study immune cells from the lining of the womb of women who have had CHI, to discover further clues as to the cause of recurrent pregnancy loss. Determining the cause of CHI is critical to the discovery of treatments that can prevent recurrence and offer affected women the hope of a healthy baby. The structure and setting of the research:The research will be divided into two components: firstly, the search for a maternal antibody that attacks the placenta in CHI; and secondly, an investigation into the function of immune cells from the endometrium (lining of the womb) in women with CHI. The first component will be undertaken at the UCL Institute for Women's Health, a vibrant community of doctors and scientists working to improve outcomes across the spectrum of women's health. The Institute hosts several high-profile related studies investigating problems such as severe fetal growth restriction and has an excellent track record in bringing innovative new maternal and fetal therapies to clinical trials. It therefore represents the perfect setting for this research. The second component will be undertaken in Sweden, thanks to an exciting collaboration with scientists at the Karolinska Institute in Stockholm. This will allow us to learn and implement pioneering new techniques for the study of endometrial immune cells and their role in placental health and disease. These cells have never been studied before in women with CHI and our findings could play a pivotal role in understanding why these women, and others, have recurrent pregnancy loss. Potential impact: This research is designed to benefit patients. Discovering the cause of CHI will bring us closer to being able to design and implement new treatments to prevent recurrent pregnancy loss. We hope that our findings could form the basis of a clinical trial for CHI in the future, and that they might also provide a useful model for the investigation of unexplained recurrent pregnancy loss. Our findings could also benefit doctors and scientists working to solve other antibody-driven diseases, such as lupus. We are committed to learning from affected patients and families about their priorities for research, their perceptions of perinatal bereavement care and their unique experience of living with a poorly understood condition that causes recurrent pregnancy loss. We want to raise the profile of this neglected disease to stimulate further research and improve outcomes for patients in the future.