{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:18:09Z","timestamp":1792815489716,"version":"4.5.0"},"reference-count":179,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["HHSN275201300006C"],"award-info":[{"award-number":["HHSN275201300006C"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Problem<\/jats:title>\n                    <jats:p>Preeclampsia is a heterogeneous syndrome of diverse etiologies and molecular pathways leading to distinct clinical subtypes. Herein, we aimed to characterize the extracellular vesicle (EV)\u2010associated and soluble fractions of the maternal plasma proteome in patients with preeclampsia and to assess their value for disease prediction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method of Study<\/jats:title>\n                    <jats:p>\n                      This case\u2013control study included 24 women with term preeclampsia, 23 women with preterm preeclampsia, and 94 healthy pregnant controls. Blood samples were collected from cases on average 7 weeks before the diagnosis of preeclampsia and were matched to control samples. Soluble and EV fractions were separated from maternal plasma; EVs were confirmed by cryo\u2010EM, NanoSight, and flow cytometry; and 82 proteins were analyzed with bead\u2010based, multiplexed immunoassays. Quantile regression analysis and random forest models were implemented to evaluate protein concentration differences and their predictive accuracy. Preeclampsia subgroups defined by molecular profiles were identified by hierarchical cluster analysis. Significance was set at\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05 or false discovery rate\u2010adjusted\n                      <jats:italic>q<\/jats:italic>\n                      &lt; 0.1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In preterm preeclampsia, PlGF, PTX3, and VEGFR\u20101 displayed differential abundance in both soluble and EV fractions, whereas angiogenin, CD40L, endoglin, galectin\u20101, IL\u201027, CCL19, and TIMP1 were changed only in the soluble fraction (\n                      <jats:italic>q<\/jats:italic>\n                      &lt; 0.1). The direction of changes in the EV fraction was consistent with that in the soluble fraction for nine proteins. In term preeclampsia, CCL3 had increased abundance in both fractions (\n                      <jats:italic>q<\/jats:italic>\n                      &lt; 0.1). The combined EV and soluble fraction proteomic profiles predicted preterm and term preeclampsia with an AUC of 78% (95% CI, 66%\u201390%) and 68% (95% CI, 56%\u201380%), respectively. Three clusters of preeclampsia featuring distinct clinical characteristics and placental pathology were identified based on combined protein data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal distinct alterations of the maternal EV\u2010associated and soluble plasma proteome in preterm and term preeclampsia and identify molecular subgroups of patients with distinct clinical and placental histopathologic features.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aji.13928","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T09:45:06Z","timestamp":1727689506000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Proteomic Profiles of Maternal Plasma Extracellular Vesicles for Prediction of Preeclampsia"],"prefix":"10.1111","volume":"92","author":[{"given":"N\u00e1ndor G\u00e1bor","family":"Than","sequence":"first","affiliation":[{"name":"Systems Biology of Reproduction Research Group Institute of Molecular Life Sciences, HUN\u2010REN Research Centre for Natural Sciences Budapest Hungary"},{"name":"Department of Obstetrics and Gynecology Semmelweis University Budapest Hungary"},{"name":"Maternity Private Clinic of Obstetrics and Gynecology Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Romero","sequence":"additional","affiliation":[{"name":"Pregnancy Research Branch Division of Obstetrics and Maternal\u2010Fetal Medicine Division of Intramural Research <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health Bethesda Maryland USA"},{"name":"Department of Obstetrics and Gynecology University of Michigan Ann Arbor Michigan USA"},{"name":"Department of 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