Histologic and molecular features shared between antibody‐mediated rejection of kidney allografts and chronic histiocytic intervillositis support common pathogenesis

• DOI: 10.1002/path.6413
• Publication Date: 2025-04-05T00:48:40Z
• Authors: Léonie Albersammer; Juliette Leon; Jelena Martinovic; Jessy Dagobert; Emilie Lebraud; Bettina Bessières; Laurence Loeuillet; Maëva Eloudzeri; Alexandre J. Vivanti; Grégoire Dumery; Valérie Marchaudon; Cristina Antal; Anne‐Sophie Korganow; Thibaud Quibel; Nathalie Costedoa...; Vassilis Tsatsaris; Alexandra Benachi; Julien Zuber; Marion Rabant
• Keywords: CD68; Immunofluorescence; Pathogenesis; Intervillous space

Chronic histiocytic intervillositis (CHI) is an inflammatory condition of the placenta, characterised by abnormal, mainly macrophagic infiltrate within intervillous space. Recent research suggests that CHI results from a 'maternal-foetal rejection' mechanism, because at least some cases fulfil criteria for antibody-mediated rejection (AMR) kidney allografts according to Banff classification [i.e. presence anti-human leukocyte antigen (HLA) paternal antibodies activating complement or foetal-specific (FSA), macrophage-rich infiltrate, and positive C4d immunostaining]. To gain further insights into pathogenesis, we aimed refine phenotype using multiplex immunofluorescence technique compare mRNA signatures between AMR allografts. Twelve patients with + FSA+ were included in study compared control group 5 without lesions on placental examination. We developed panel identify CD4+ CD8+ T lymphocytes, CD68+/CD206- CD68+/CD206+ macrophages, NK cells villi Molecular studied NanoString® technology B-HOT recommended Multiplex revealed space was composed macrophages as well higher proportion lymphocytes controls. Densities CD4 very low. showed overexpression HLA class II genes, IFN-γ signature, cytokine gene sets patients, also involved AMR. These reinforce paradigm maternal-foetal rejection. © 2025 The Author(s). Journal Pathology published John Wiley & Sons Ltd behalf Pathological Society Great Britain Ireland.