The Obstetrics and Gynecology Department, Groupe Hospitalier Pellegrin, Bordeaux University Hospital, Bordeaux, France.
Fœtopathology Unit, Pathology Department, Groupe Hospitalier Pellegrin, Bordeaux University Hospital, Bordeaux, France.
Nat Commun. 2024 Oct 30;15(1):9396. doi: 10.1038/s41467-024-53591-w.
Chronic histiocytic intervillositis of unknown origin (CHI) is a rare placental disorder associated with adverse pregnancy outcomes, frequent recurrence, and a lack of effective preventive strategies. Recent insights indicate a potential link between CHI-associated inflammatory lesions and the inflammasome pathway, suggesting innovative therapeutic avenues. Here we show a potential role of the inflammasome pathway in CHI through comprehensive transcriptomic analysis of grade 2 or 3 histopathologic CHI samples, paired with placental controls. Additionally, we present case studies of three individuals with recurrent CHI, who have undergone treatment with anakinra and colchicine throughout pregnancy, resulting in improved perinatal outcomes. Notably, all cases are characterized by the birth of healthy, full-term infants, with reduced or absent intervillositis recurrence. Placental assessment unveils heightened activation of the NLRP3-PYCARD inflammasome pathway and IL-1β processing in CHI samples, with downregulation observed in treated pregnancy samples, devoid of intervillositis. Collectively, these findings suggest a potential therapeutic role for targeting the inflammasome pathway in preventing recurrent CHI in pregnant individuals.
原因不明的慢性组织细胞绒毛膜炎（CHI）是一种罕见的胎盘疾病，与不良妊娠结局、频繁复发以及缺乏有效预防策略有关。最近的研究表明，CHI 相关炎症病变与炎症小体途径之间可能存在关联，这为创新的治疗方法提供了线索。在这里，我们通过对 2 级或 3 级组织病理学 CHI 样本进行全面转录组分析，并与胎盘对照进行配对，展示了炎症小体途径在 CHI 中的潜在作用。此外，我们还介绍了 3 名复发性 CHI 患者的病例研究，他们在整个怀孕期间接受了阿那白滞素和秋水仙碱治疗，从而改善了围产期结局。值得注意的是，所有病例的特点是均足月分娩出健康婴儿，且绒毛膜炎复发率降低或消失。胎盘评估揭示了 CHI 样本中 NLRP3-PYCARD 炎症小体途径和 IL-1β 加工的高度激活，而在未出现绒毛膜炎的治疗妊娠样本中观察到下调。总之，这些发现表明，针对炎症小体途径可能在预防孕妇复发性 CHI 中具有潜在的治疗作用。
