Inflammasome-targeted therapy might prevent adverse perinatal outcomes of recurrent chronic intervillositis of unknown etiology
Aurélien Mattuizzi, Fanny Sauvestre, Tiphaine Fargeix, Eoghann White, Claire Leibler, Marine Cargou, Nathalie Dugot‐Senant, Isabelle Douchet, Dorothée Duluc, Cécile Bordes, Marie‐Elise Truchetet, Christophe Richez, Édouard Forcade, P. Duffau, Jean‐François Viallard, Loı̈c Sentilhes, Patrick Blanco, Estibaliz Lazaro
Abstract
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. Chronic histiocytic intervillositis of unknown origin is a rare but serious and hard-to-prevent condition, leading to repeated pregnancy losses. Here authors show that high-grade cases are associated with inflammasome activation in placental samples, and they report the birth of healthy full-term infants following sustained inflammasome inhibition in three high-risk pregnancies.