{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T23:14:06Z","timestamp":1784675646672,"version":"3.55.0"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 \u2018maternal\u2010foetal rejection\u2019 mechanism, because at least some CHI cases fulfil the criteria for antibody\u2010mediated rejection (AMR) of kidney allografts according to the Banff classification [i.e. presence of anti\u2010human leukocyte antigen (HLA) paternal antibodies activating the complement or foetal\u2010specific antibodies (FSA), a macrophage\u2010rich 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+\u2009FSA+ 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\u2212 and CD68+\/CD206+ macrophages, and NK cells in the villi and intervillous space. Molecular signatures were studied using NanoString\u00ae technology and the B\u2010HOT 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\u2212 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\u2010\u03b3 signature, and cytokine gene sets in C4d+\u2009FSA+ CHI patients, also involved in kidney AMR. These results reinforce the paradigm of maternal\u2010foetal rejection. \u00a9 2025 The Author(s). <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6413","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T20:48:40Z","timestamp":1743799720000},"page":"177-191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Histologic and molecular features shared between antibody\u2010mediated rejection of kidney allografts and chronic histiocytic intervillositis support common pathogenesis"],"prefix":"10.1002","volume":"266","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3722-5598","authenticated-orcid":false,"given":"L\u00e9onie","family":"Albersammer","sequence":"first","affiliation":[{"name":"Department of Pathology Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Necker  Paris France"},{"name":"Department of Obstetrics and Gynecology H\u00f4pital Antoine B\u00e9cl\u00e8re, AP\u2010HP, Universit\u00e9 Paris Saclay  Clamart France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5314-8154","authenticated-orcid":false,"given":"Juliette","family":"Leon","sequence":"additional","affiliation":[{"name":"Department of Kidney and Metabolic Diseases Transplantation and Clinical Immunology, Necker Hospital, AP\u2010HP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4595-7271","authenticated-orcid":false,"given":"Jelena","family":"Martinovic","sequence":"additional","affiliation":[{"name":"Unit of Embryo\u2010Fetal Pathology, AP\u2010HP, Antoine B\u00e9cl\u00e8re Hospital, Paris Saclay University  Clamart France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessy","family":"Dagobert","sequence":"additional","affiliation":[{"name":"Paris Translational Research Epidemiology and Biostatistics Department, Universit\u00e9 de Paris, INSERM U970, PARCC  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8092-3197","authenticated-orcid":false,"given":"Emilie","family":"Lebraud","sequence":"additional","affiliation":[{"name":"Necker\u2010Enfants Malades Institute, Inserm U1151, Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Bessi\u00e8res","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies Rares UF MP5 H\u00f4pital Necker\u2010Enfants Malades, AP\u2010HP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Loeuillet","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies Rares UF MP5 H\u00f4pital Necker\u2010Enfants Malades, AP\u2010HP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u00ebva","family":"Eloudzeri","sequence":"additional","affiliation":[{"name":"Necker\u2010Enfants Malades Institute, Inserm U1151, Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4921-0047","authenticated-orcid":false,"given":"Alexandre J.","family":"Vivanti","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology H\u00f4pital Antoine B\u00e9cl\u00e8re, AP\u2010HP, Universit\u00e9 Paris Saclay  Clamart France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9goire","family":"Dumery","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology AP\u2010HP, H\u00f4pital Bic\u00eatre  Le Kremlin\u2010Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Marchaudon","sequence":"additional","affiliation":[{"name":"Centre hospitalier du Sud Seine\u2010et\u2010Marne  Fontainebleau France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8331-5520","authenticated-orcid":false,"given":"Cristina","family":"Antal","sequence":"additional","affiliation":[{"name":"H\u00f4pitaux Universitaires de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1664-6311","authenticated-orcid":false,"given":"Anne\u2010Sophie","family":"Korganow","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Internal Medicine National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiency, Strasbourg University Hospital  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaud","family":"Quibel","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Internal Medicine National Reference Center for Autoimmune Diseases, University Hospitals of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1555-9021","authenticated-orcid":false,"given":"Nathalie","family":"Costedoat\u2010Chalumeau","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine H\u00f4pital Cochin  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilis","family":"Tsatsaris","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Port Royal H\u00f4pital Cochin, Universit\u00e9 de Paris\/AP\u2010HP, Fighting Prematurity University Hospital Federation (FHU PREMA), INSERM UMR 1139  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-0765","authenticated-orcid":false,"given":"Alexandra","family":"Benachi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology H\u00f4pital Antoine B\u00e9cl\u00e8re, AP\u2010HP, Universit\u00e9 Paris Saclay  Clamart France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6741-9330","authenticated-orcid":false,"given":"Julien","family":"Zuber","sequence":"additional","affiliation":[{"name":"Department of Kidney and Metabolic Diseases Transplantation and Clinical Immunology, Necker Hospital, AP\u2010HP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5696-6478","authenticated-orcid":false,"given":"Marion","family":"Rabant","sequence":"additional","affiliation":[{"name":"Department of Pathology Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Necker  Paris France"},{"name":"Necker\u2010Enfants Malades Institute, Inserm U1151, Universit\u00e9 de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.642392"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2021-0296-SA"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.1987.tb00162.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2017.11.012"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.825075"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/apm.12796"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13373"},{"key":"e_1_2_8_9_1","first-page":"1103","article-title":"Expression analysis of leukocytes attracting cytokines in chronic histiocytic intervillositis of the placenta","volume":"6","author":"Freitag L","year":"2013","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2021.06.051"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2022.11.014"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-69191-9"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001549"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/08916934.2014.939267"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2010.11.021"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2010.10.005"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(00)80009-X"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2016-217886"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.753220"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12143"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12125"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15898"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.2350\/14-12-1582-OA.1"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1901297"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12048"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15699"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13942-8"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep09534"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16059"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.04.015"},{"key":"e_1_2_8_31_1","first-page":"120","article-title":"Modulators of the balance between M1 and M2 macrophages during pregnancy","volume":"8","author":"Zhang Y\u2010H","year":"2017","journal-title":"Front Immunol"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065300"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1220030"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.10.6322-6331.2005"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1095879"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2019.02.007"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2022-0494-OA"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2023.05.007"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.10.041"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-019-00101-9"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-51545-2"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0698-6"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21134756"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00696-7"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0378(01)00115-2"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI95937"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-69315-5"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014080797"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-70390-x"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-021-02691-9"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12946"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2400763"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000002912"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000000000192"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac762"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.90"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12542"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009753"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38628"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2667"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.6413","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T09:22:38Z","timestamp":1761038558000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.6413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,3]]},"references-count":59,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/path.6413"],"URL":"https:\/\/doi.org\/10.1002\/path.6413","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,3]]},"assertion":[{"value":"2024-08-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}