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