{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:47:55Z","timestamp":1756190875234,"version":"3.41.2"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Preeclampsia, a multifaceted condition during pregnancy characterized by hypertension and organ dysfunction, poses significant risks to both maternal and fetal health. This study aims to investigate the bidirectional causal relationship between peripheral immune cell phenotypes and preeclampsia using a two\u2010sample Mendelian randomization (MR) approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>Genetic data from two sizable cohorts were utilized: 3757 individuals from Sardinia, providing information on 731 immune traits, and 200\u00a0929 Finnish adult females, encompassing 6663 preeclampsia cases. Single\u2010nucleotide polymorphisms served as instrumental variables. The MR analyses employed the inverse variance\u2010weighted (IVW) method as the primary tool, supplemented by MR\u2010Egger, weighted median, and weighted mode methods to enhance reliability and address potential heterogeneity and horizontal pleiotropy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 731 immune cell phenotypes studied, 18 displayed a suggestive positive association (IVW <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) with heightened preeclampsia risk, while 20 exhibited a suggestive negative association linked to reduced risk. Following false discovery rate (FDR) adjustment, four immune phenotypes showed significant associations with decreased preeclampsia risk: CD27 on CD24+ CD27+ B cells (B\u2010cell panel) (odds ratio [OR]\u00a0=\u00a00.927, P<jats:sub>FDR\u00a0<\/jats:sub>=\u00a00.061), CD33+ HLA DR+ CD14\u2212 absolute count (OR\u00a0=\u00a00.963, P<jats:sub>FDR\u00a0<\/jats:sub>=\u00a00.061), CD80 on plasmacytoid dendritic cells (OR\u00a0=\u00a00.923, P<jats:sub>FDR\u00a0<\/jats:sub>=\u00a00.061); and CD80 on CD62L+ plasmacytoid dendritic cells (OR\u00a0=\u00a00.923, P<jats:sub>FDR\u00a0<\/jats:sub>=\u00a00.061). In the reverse\u2010direction MR analysis, no significant causal effects of preeclampsia on immune cell phenotypes were observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study provides quantifiable evidence linking specific immune cell phenotypes to the risk of developing preeclampsia. This novel understanding of the immunological aspects underlying preeclampsia's pathogenesis could lead to innovative therapeutic strategies centered on immune modulation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13840","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T10:39:25Z","timestamp":1712918365000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigating causal relationships between extensive peripheral immune cell phenotypes and preeclampsia: A bi\u2010directional Mendelian randomization analysis"],"prefix":"10.1111","volume":"91","author":[{"given":"Chung\u2010Chih","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Post\u2010Baccalaureate Veterinary Medicine College of Medical and Health Science, Asia University  Taichung Taiwan"},{"name":"Chuyuan Chinese Medicine Clinic  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju\u2010Chun","family":"Ku","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, College of Chinese Medicine, China Medical University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Li","family":"Lin","sequence":"additional","affiliation":[{"name":"Management Office for Health Data China Medical University Hospital  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju\u2010Wan","family":"Li","sequence":"additional","affiliation":[{"name":"Anxin Postpartum Nursing Home, Lee Women's Hospital  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuu\u2010Jen","family":"Tsai","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, College of Chinese Medicine, China Medical University  Taichung Taiwan"},{"name":"Department of Medical Research China Medical University Hospital  Taichung Taiwan"},{"name":"Division of Medical Genetics China Medical University Children's Hospital  Taichung Taiwan"},{"name":"Department of Biotechnology and Bioinformatics Asia University  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7069-8510","authenticated-orcid":false,"given":"Jung\u2010Miao","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, College of Chinese Medicine, China Medical University  Taichung Taiwan"},{"name":"Department of Chinese Medicine China Medical University Hospital  Taichung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"7","article-title":"Risk factors and effective management of preeclampsia","volume":"8","author":"English FA","year":"2015","journal-title":"Integr Blood Press Control"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8101625"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c200008"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-017-0757-7"},{"issue":"4","key":"e_1_2_9_6_1","first-page":"309","article-title":"Endothelial dysfunction. 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