Elizabeth Garrett Anderson Institute for Women's Health, Department of Maternal and Fetal Medicine, University College London, London, United Kingdom.
Faculty of Engineering Science, Department of Biochemical Engineering, University College London, London, United Kingdom.
Front Immunol. 2022 Apr 22;13:825075. doi: 10.3389/fimmu.2022.825075. eCollection 2022.
Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these three chronic inflammatory placental syndromes.
慢性炎症性胎盘疾病是一组罕见但具有破坏性的妊娠综合征，与不良妊娠结局相关。本综述重点介绍三种相关疾病：原因不明的绒毛膜炎（VUE）、慢性组织细胞性绒毛膜炎（CHI）和绒毛膜外大量纤维蛋白沉积（MPFD）。这些疾病的标志是母体免疫细胞浸润胎盘结构并破坏绒毛间隙，胎儿和母体在此处进行气体交换。目前，只有在妊娠结束后通过胎盘的组织病理学检查才能发现这些疾病。所有三种疾病在随后的妊娠中都有显著的复发风险。原因不明的绒毛膜炎的特征是母体 CD8+T 淋巴细胞破坏性浸润绒毛，同时激活胎儿绒毛膜巨噬细胞。只有在排除感染病因后才能做出诊断。随着妊娠的进展，VUE 变得更为常见，并且通常与正常妊娠结局相关。然而，严重的早发型绒毛膜炎通常与胎儿生长受限和反复流产相关。慢性组织细胞性绒毛膜炎的特征是绒毛间隙中母体 CD68+组织细胞过度积聚。它与广泛的不良妊娠结局相关，包括早期流产、严重胎儿生长受限和晚期宫内胎儿死亡。绒毛间隙中的组织细胞也可能因感染而积聚，包括 SARS-CoV-2，但这种感染引起的绒毛膜炎似乎不会复发。与 VUE 一样，CHI 的诊断需要排除感染原因。反复发生 CHI 的女性及其家庭易患自身免疫性疾病，这表明 CHI 可能具有同种免疫病理学。这一观察结果促使人们尝试使用各种母体免疫抑制来预防 CHI。当绒毛间隙中超过 25%的空间被纤维蛋白占据时，即可诊断为大量绒毛膜外纤维蛋白沉积，并与胎儿生长受限和晚期宫内胎儿死亡相关。虽然本身不是炎症性疾病，但 MPFD 常与 VUE 和 CHI 相关。本综述总结了目前对这三种慢性炎症性胎盘综合征的患病率、诊断特征、临床后果、免疫病理学以及潜在的复发预防措施的认识。
