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妊娠疾病的原因，这种疾病会导致反复流产和死产。慢性组织细胞性间隔炎(CHI)影响着每10,000名孕妇中的1名，但复发的风险非常高，这意味着一些受影响的夫妇已经遭受了几次妊娠损失。在CHI怀孕的所有婴儿中，只有大约一半存活下来，其中超过一半的婴儿将非常早产，对他们的健康造成长期后果。对于承受这些反复损失的父母来说，情感负担是巨大的。我们选择研究这种疾病，希望改善受影响家庭的前景。CHI的原因尚不清楚，只有在怀孕结束后才能通过在显微镜下分析胎盘来诊断。在随后的怀孕中，除了在超声波扫描上识别出一个非常小的婴儿外，还没有得到证实的复发警告迹象，也没有可靠的测试可以预测怀孕成功或失败。也没有治疗方法可以始终如一地防止CHI复发。该项目的主要目标：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，并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病因的理解。我还将研究患有CHI的妇女子宫内壁的免疫细胞，以找到关于反复妊娠丢失原因的进一步线索。确定CHI的原因对于发现可以防止复发并为受影响的妇女带来健康婴儿的希望的治疗方法至关重要。研究的结构和背景：研究将分为两个部分：第一，寻找攻击CHI胎盘的母体抗体；第二，调查CHI患者子宫内膜(子宫内壁)免疫细胞的功能。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领域的成果。该研究所主持了几项备受瞩目的相关研究，调查严重的胎儿生长受限等问题，并在将创新的产妇和胎儿治疗方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研究子宫内膜免疫细胞及其在胎盘健康和疾病中的作用的开创性新技术。这些细胞以前从未在CHI女性身上进行过研究，我们的发现可能对理解这些女性和其他人反复妊娠丢失的原因起到关键作用。潜在影响：这项研究旨在使患者受益。发现CHI的病因将使我们更接近于能够设计和实施新的治疗方法来防止反复妊娠丢失。我们希望我们的发现可以成为未来CHI临床试验的基础，也可能为不明原因的反复妊娠丢失的研究提供一个有用的模型。我们的发现也可能使致力于解决其他抗体驱动的疾病的医生和科学家受益，例如狼疮。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，以及他们在导致反复妊娠丢失的情况下生活在鲜为人知的情况下的独特经历。我们希望提高这种被忽视的疾病的知名度，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.