{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T14:25:53Z","timestamp":1789223153783,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005039","name":"Leids Universitair Medisch Centrum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005039","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HLA"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>In pregnancy, semi\u2010allogenic foetal trophoblasts express a specific HLA profile mediating maternal leukocyte contact, crucial for placentation. Paradoxically, maternal immunomodulation requires foetal antigen recognition, especially involving certain HLA molecules. Pre\u2010eclampsia, a severe hypertensive complication, has been linked to antigenic similarity. Previously, we showed no selection for HLA (in)compatibility in uncomplicated naturally conceived pregnancies. However, pre\u2010eclamptic pregnancies were associated with increased total maternal\u2013foetal HLA and HLA\u2010C matching. These associations suggest a role for HLA mismatches in immune regulation leading to an uncomplicated pregnancy. To better understand HLA homozygosity in human reproduction, we aimed to determine if there is a preferential selection for HLA compatibility in a genetically isolated population, and its relation to hypertensive complications. A nested case\u2010control study, comprising 125 uncomplicated pregnancies and 50 with hypertensive complications (29 with pregnancy\u2010induced hypertension, 21 with pre\u2010eclampsia) was conducted in a genetically isolated Dutch population (F<jats:sub>ROH<\/jats:sub> 1.3\u20133.1). Maternal and foetal HLA\u2010A, \u2010B, \u2010C, \u2010DRB1, \u2010DQA1, \u2010DQB1 and maternal killer\u2010cell immunoglobulin\u2010like receptor (KIR) genotyping were performed. Maternal\u2013foetal HLA (mis)match counts were compared to expected values from randomisation of paternal HLA haplotypes over maternal haplotypes of the foetuses. Mismatched CD4<jats:sup>+<\/jats:sup> T cell epitopes presented by maternal HLA class II were predicted using the PIRCHE\u2010II algorithm. In uncomplicated pregnancies, no difference was found between observed and expected maternal\u2013foetal HLA (mis)matches. However, pregnancies with hypertensive complications showed significantly higher observed HLA\u2010DQB1 mismatches, reflected in PIRCHE\u2010II scores. No significant differences were found in KIR\/HLA\u2010C frequencies. Interpretation is limited by the small sample size and the grouping of distinct hypertensive disorders. Nonetheless, maternal\u2013foetal HLA\u2010DQB1 mismatch seems to play a role in the aetiology of hypertensive complications during pregnancy in this population.<\/jats:p>","DOI":"10.1111\/tan.70374","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T08:10:17Z","timestamp":1755850217000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Maternal\u2013Foetal <scp>HLA<\/scp>\u2010<scp>DQB1<\/scp> Incompatibility Is Associated With Pregnancy\u2010Induced Hypertensive Disorders in a Genetically Isolated Population"],"prefix":"10.1111","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1756-3825","authenticated-orcid":false,"given":"Liseanne J. van\u2019t","family":"Hof","sequence":"first","affiliation":[{"name":"Department of Immunology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Louise P.","family":"van der Hoorn","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selena","family":"Migdis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert W.","family":"Haasnoot","sequence":"additional","affiliation":[{"name":"Department of Immunology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma T. M.","family":"Peereboom","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology University Medical Center Utrecht  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9441-1019","authenticated-orcid":false,"given":"Eric","family":"Spierings","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology University Medical Center Utrecht  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter J. E.","family":"van der Linden","sequence":"additional","affiliation":[{"name":"Department of Immunology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline D. 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