用于预测子痫前期的母体血浆细胞外囊泡蛋白质组图谱。

IF 2.5 3区 医学 Q3 IMMUNOLOGY American Journal of Reproductive Immunology Pub Date : 2024-09-30 DOI:10.1111/aji.13928
Nándor Gábor Than, Roberto Romero, Wendy Fitzgerald, Dereje W. Gudicha, Nardhy Gomez-Lopez, Máté Posta, Fei Zhou, Gaurav Bhatti, Arun Meyyazhagan, Awoniyi O. Awonuga, Tinnakorn Chaiworapongsa, Doreen Matthies, David R. Bryant, Offer Erez, Leonid Margolis, Adi L. Tarca
{"title":"用于预测子痫前期的母体血浆细胞外囊泡蛋白质组图谱。","authors":"Nándor Gábor Than,&nbsp;Roberto Romero,&nbsp;Wendy Fitzgerald,&nbsp;Dereje W. Gudicha,&nbsp;Nardhy Gomez-Lopez,&nbsp;Máté Posta,&nbsp;Fei Zhou,&nbsp;Gaurav Bhatti,&nbsp;Arun Meyyazhagan,&nbsp;Awoniyi O. Awonuga,&nbsp;Tinnakorn Chaiworapongsa,&nbsp;Doreen Matthies,&nbsp;David R. Bryant,&nbsp;Offer Erez,&nbsp;Leonid Margolis,&nbsp;Adi L. Tarca","doi":"10.1111/aji.13928","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Problem</h3>\n \n <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)-associated and soluble fractions of the maternal plasma proteome in patients with preeclampsia and to assess their value for disease prediction.</p>\n </section>\n \n <section>\n \n <h3> Method of Study</h3>\n \n <p>This case–control 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-EM, NanoSight, and flow cytometry; and 82 proteins were analyzed with bead-based, 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 <i>p</i> &lt; 0.05 or false discovery rate-adjusted <i>q</i> &lt; 0.1.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>In preterm preeclampsia, PlGF, PTX3, and VEGFR-1 displayed differential abundance in both soluble and EV fractions, whereas angiogenin, CD40L, endoglin, galectin-1, IL-27, CCL19, and TIMP1 were changed only in the soluble fraction (<i>q</i> &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 (<i>q</i> &lt; 0.1). The combined EV and soluble fraction proteomic profiles predicted preterm and term preeclampsia with an AUC of 78% (95% CI, 66%–90%) and 68% (95% CI, 56%–80%), respectively. Three clusters of preeclampsia featuring distinct clinical characteristics and placental pathology were identified based on combined protein data.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Our findings reveal distinct alterations of the maternal EV-associated and soluble plasma proteome in preterm and term preeclampsia and identify molecular subgroups of patients with distinct clinical and placental histopathologic features.</p>\n </section>\n </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 4","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.13928","citationCount":"0","resultStr":"{\"title\":\"Proteomic Profiles of Maternal Plasma Extracellular Vesicles for Prediction of Preeclampsia\",\"authors\":\"Nándor Gábor Than,&nbsp;Roberto Romero,&nbsp;Wendy Fitzgerald,&nbsp;Dereje W. Gudicha,&nbsp;Nardhy Gomez-Lopez,&nbsp;Máté Posta,&nbsp;Fei Zhou,&nbsp;Gaurav Bhatti,&nbsp;Arun Meyyazhagan,&nbsp;Awoniyi O. Awonuga,&nbsp;Tinnakorn Chaiworapongsa,&nbsp;Doreen Matthies,&nbsp;David R. Bryant,&nbsp;Offer Erez,&nbsp;Leonid Margolis,&nbsp;Adi L. Tarca\",\"doi\":\"10.1111/aji.13928\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Problem</h3>\\n \\n <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)-associated and soluble fractions of the maternal plasma proteome in patients with preeclampsia and to assess their value for disease prediction.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Method of Study</h3>\\n \\n <p>This case–control 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-EM, NanoSight, and flow cytometry; and 82 proteins were analyzed with bead-based, 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 <i>p</i> &lt; 0.05 or false discovery rate-adjusted <i>q</i> &lt; 0.1.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>In preterm preeclampsia, PlGF, PTX3, and VEGFR-1 displayed differential abundance in both soluble and EV fractions, whereas angiogenin, CD40L, endoglin, galectin-1, IL-27, CCL19, and TIMP1 were changed only in the soluble fraction (<i>q</i> &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 (<i>q</i> &lt; 0.1). The combined EV and soluble fraction proteomic profiles predicted preterm and term preeclampsia with an AUC of 78% (95% CI, 66%–90%) and 68% (95% CI, 56%–80%), respectively. Three clusters of preeclampsia featuring distinct clinical characteristics and placental pathology were identified based on combined protein data.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Our findings reveal distinct alterations of the maternal EV-associated and soluble plasma proteome in preterm and term preeclampsia and identify molecular subgroups of patients with distinct clinical and placental histopathologic features.</p>\\n </section>\\n </div>\",\"PeriodicalId\":7665,\"journal\":{\"name\":\"American Journal of Reproductive Immunology\",\"volume\":\"92 4\",\"pages\":\"\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.13928\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Reproductive Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/aji.13928\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Reproductive Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/aji.13928","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

问题:子痫前期是一种异质性综合征,其病因和分子途径各不相同,导致不同的临床亚型。在此,我们旨在描述子痫前期患者母体血浆蛋白质组中细胞外囊泡(EV)相关部分和可溶性部分的特征,并评估其对疾病预测的价值:这项病例对照研究包括24名足月子痫前期妇女、23名早产子痫前期妇女和94名健康孕妇对照组。病例平均在确诊子痫前期前 7 周采集血样,并与对照组血样进行比对。从母体血浆中分离出可溶性部分和 EV 部分;通过低温电子显微镜、NanoSight 和流式细胞术确认了 EV;通过基于微珠的多重免疫测定分析了 82 种蛋白质。采用量子回归分析和随机森林模型评估蛋白质浓度差异及其预测准确性。通过分层聚类分析确定了由分子特征定义的子痫前期亚组。显著性设定为 p < 0.05 或假发现率调整后的 q < 0.1:结果:在先兆子痫患者中,PlGF、PTX3和VEGFR-1在可溶部分和EV部分的丰度不同,而血管生成素、CD40L、内凝血酶原、galectin-1、IL-27、CCL19和TIMP1仅在可溶部分发生变化(q < 0.1)。9种蛋白质在EV部分的变化方向与在可溶性部分的变化方向一致。在子痫前期,CCL3 在两个馏分中的丰度都增加了(q < 0.1)。EV和可溶性部分蛋白质组组合图谱预测早产和足月子痫前期的AUC分别为78%(95% CI,66%-90%)和68%(95% CI,56%-80%)。根据合并的蛋白质数据,确定了具有不同临床特征和胎盘病理学的三个子痫前期群组:我们的研究结果揭示了早产和足月子痫前期母体EV相关和可溶性血浆蛋白质组的不同变化,并确定了具有不同临床和胎盘组织病理学特征的分子亚组。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Proteomic Profiles of Maternal Plasma Extracellular Vesicles for Prediction of Preeclampsia

Problem

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)-associated and soluble fractions of the maternal plasma proteome in patients with preeclampsia and to assess their value for disease prediction.

Method of Study

This case–control 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-EM, NanoSight, and flow cytometry; and 82 proteins were analyzed with bead-based, 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 p < 0.05 or false discovery rate-adjusted q < 0.1.

Results

In preterm preeclampsia, PlGF, PTX3, and VEGFR-1 displayed differential abundance in both soluble and EV fractions, whereas angiogenin, CD40L, endoglin, galectin-1, IL-27, CCL19, and TIMP1 were changed only in the soluble fraction (q < 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 (q < 0.1). The combined EV and soluble fraction proteomic profiles predicted preterm and term preeclampsia with an AUC of 78% (95% CI, 66%–90%) and 68% (95% CI, 56%–80%), respectively. Three clusters of preeclampsia featuring distinct clinical characteristics and placental pathology were identified based on combined protein data.

Conclusions

Our findings reveal distinct alterations of the maternal EV-associated and soluble plasma proteome in preterm and term preeclampsia and identify molecular subgroups of patients with distinct clinical and placental histopathologic features.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
6.20
自引率
5.60%
发文量
314
审稿时长
2 months
期刊介绍: The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.
期刊最新文献
Issue Information Impact of Omicron Variant Infection on Female Fertility and Laboratory Outcomes: A Self-Controlled Study Cell Communications Between GCs and Macrophages Contribute to the Residence of Macrophage in Preovulatory Follicles Immune Thrombocytopenic Purpura and Maternal and Neonatal Outcomes During Pregnancy: A Systematic Review and Meta-Analysis Association of Systemic Inflammatory Indices and Last Trimester APRI Score With Perinatal Outcomes in Pregnant Women With Pregestational Diabetes-A Prospective Observational Study.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1