{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T16:47:21Z","timestamp":1772642841690,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality, yet its pathophysiology is not fully understood. Recent studies suggest that dysregulated maternal immune responses, particularly involving decidual Natural Killer (dNK) cells and immune checkpoint molecules such as B7-H3, may play a role in the pathogenesis of this heterogeneous syndrome, particularly in the development of early-onset preeclampsia (EOP). Objective: The aim of this study was to investigate the expression patterns of B7-H3 on extravillous trophoblasts (EVTs) and the abundance of dNK cells in preeclamptic versus normotensive pregnancies and to analyze the relationship between these two immune parameters. Methods: A cross-sectional study was conducted using 42 placental samples (21 preeclampsia, 21 controls). Immunohistochemistry (IHC) was performed to detect CD56 (dNK cells) and CD276 (B7-H3) expression. Expression was semi-quantitatively evaluated using the Remmele Immunoreactive Score (IRS). Statistical comparisons and correlation analyses were conducted. Results: Preeclamptic placentas exhibited significantly higher dNK cell expression (IRS 7.19 \u00b1 2.16) and significantly lower B7-H3 expression (IRS 2.63 \u00b1 0.90) compared to controls (p &lt; 0.001 and p = 0.002, respectively). A positive correlation was found between B7-H3 and dNK cell expression in both groups, with a stronger correlation in normotensive pregnancies (r = 0.605; p = 0.004) and preeclampsia (r = 0.465; p = 0.034). Conclusions: The inverse expression pattern and reduction in B7-H3 expression compared to dNK cells in preeclampsia suggest a loss of immune tolerance at the maternal\u2013fetal interface. These findings highlight the potential of B7-H3 as a biomarker and immunoregulatory target for early prediction and prevention of preeclampsia.<\/jats:p>","DOI":"10.3390\/medsci13040239","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T02:03:48Z","timestamp":1761185028000},"page":"239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunoregulatory Imbalance in Preeclampsia: A Cross-Sectional Study of B7-H3 and Decidual NK Cell Interactions"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5050-2370","authenticated-orcid":false,"given":"Khanisyah Erza","family":"Gumilar","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Universitas Airlangga Hospital, Surabaya 60115, Indonesia"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander Indra","family":"Humala","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"},{"name":"Department of Obstetrics and Gynecology, Indonesia Army Central Hospital Gatot Soebroto, Jakarta 10410, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8013-4639","authenticated-orcid":false,"given":"Manggala Pasca","family":"Wardhana","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"},{"name":"Department of Obstetrics and Gynecology, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9344-3606","authenticated-orcid":false,"given":"Ernawati","family":"Ernawati","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"},{"name":"Department of Obstetrics and Gynecology, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agus","family":"Sulistyono","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"},{"name":"Department of Obstetrics and Gynecology, Dr. Soetomo General Academic Hospital, Surabaya 60286, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6060-9190","authenticated-orcid":false,"given":"Budi","family":"Utomo","sequence":"additional","affiliation":[{"name":"Department of Public Health and Preventive Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Ariani","sequence":"additional","affiliation":[{"name":"Department of Pathology Anatomy, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2007-9898","authenticated-orcid":false,"given":"Ming","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"},{"name":"Graduate Institute of Biomedical Science, China Medical University, Taichung 40402, Taiwan"},{"name":"Institute of Biochemistry and Molecular Biology and Research Center for Cancer Biology, China Medical University, Taichung 406040, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erry Gumilar","family":"Dachlan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gus","family":"Dekker","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"},{"name":"Department of Obstetrics and Gynecology, Lyell McEwin Hospital, University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41572-023-00417-6","article-title":"Pre-eclampsia","volume":"9","author":"Dimitriadis","year":"2023","journal-title":"Nat. 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