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-Élise Truchetet, Christophe Richez, Édouard Forcade, Pierre Duffau, Jean-François Viallard, Loïc Sentilhes, Patrick Blanco and Estibaliz Lazaro ()
Additional contact information
Aurélien Mattuizzi: Bordeaux University Hospital
Fanny Sauvestre: Bordeaux University Hospital
Tiphaine Fargeix: Bordeaux University Hospital
Eoghann White: Bordeaux University
Claire Leibler: Bordeaux University
Marine Cargou: Bordeaux University Hospital
Nathalie Dugot-Senant: TBM-Core US 005
Isabelle Douchet: Bordeaux University
Dorothée Duluc: Bordeaux University
Cécile Bordes: Bordeaux University
Marie-Élise Truchetet: Bordeaux University
Christophe Richez: Bordeaux University
Édouard Forcade: Bordeaux University
Pierre Duffau: Bordeaux University
Jean-François Viallard: Bordeaux University Hospital
Loïc Sentilhes: Bordeaux University Hospital
Patrick Blanco: Bordeaux University
Estibaliz Lazaro: Bordeaux University Hospital

Nature Communications, 2024, vol. 15, issue 1, 1-9

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53591-w

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