Pregnancy complications such as spontaneous abortion, preeclampsia, and preterm birth persist, despite current interventions aimed at their prevention and treatment largely proving unsuccessful. Interleukin-27 (IL-27), composed of p28 and EBI3 subunits, binds to IL-27R, which consists of gp130 and IL-27Rα (also known as WSX-1 or TCCR), and plays a pivotal role in tumor development and inflammation regulation. At the maternal-fetal interface, IL-27 expression has been detected in trophoblasts, endometrial stromal cells, and decidual cells. Abnormal levels of IL-27/IL-27R have been linked to adverse pregnancy outcomes, including spontaneous miscarriage, preeclampsia, and preterm birth. This review aims to explore the expression of IL-27 at the maternal-fetal interface and its signaling pathway, uncovering the complex role of IL-27 in pregnancy complications.
Method of Study
A comprehensive literature review was conducted using PubMed/Medline, Scopus, and Embase databases, analyzing studies on IL-27 expression and its signaling pathways at the maternal-fetal interface. The review focused on identifying the presence of IL-27 in various cell types and linking abnormal IL-27/IL-27R expression to pregnancy complications such as spontaneous miscarriage, preeclampsia, and preterm birth.
Discussion and Conclusion
IL-27 plays a complex role at the maternal-fetal interface, with abnormal expression linked to several pregnancy complications. These findings highlight the need for further research to elucidate IL-27's mechanisms and develop targeted interventions. Future studies should aim to develop targeted interventions and improve therapeutic strategies for managing pregnancy complications.
{"title":"Emerging Roles of IL-27 in Trophoblast Cells and Pregnancy Complications","authors":"Yi-Hua Luo, Yang-Yang Zhang, Ming-Qing Li, Xin-Yan Zhang, Zi-Meng Zheng","doi":"10.1111/aji.13942","DOIUrl":"https://doi.org/10.1111/aji.13942","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Pregnancy complications such as spontaneous abortion, preeclampsia, and preterm birth persist, despite current interventions aimed at their prevention and treatment largely proving unsuccessful. Interleukin-27 (IL-27), composed of p28 and EBI3 subunits, binds to IL-27R, which consists of gp130 and IL-27Rα (also known as WSX-1 or TCCR), and plays a pivotal role in tumor development and inflammation regulation. At the maternal-fetal interface, IL-27 expression has been detected in trophoblasts, endometrial stromal cells, and decidual cells. Abnormal levels of IL-27/IL-27R have been linked to adverse pregnancy outcomes, including spontaneous miscarriage, preeclampsia, and preterm birth. This review aims to explore the expression of IL-27 at the maternal-fetal interface and its signaling pathway, uncovering the complex role of IL-27 in pregnancy complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>A comprehensive literature review was conducted using PubMed/Medline, Scopus, and Embase databases, analyzing studies on IL-27 expression and its signaling pathways at the maternal-fetal interface. The review focused on identifying the presence of IL-27 in various cell types and linking abnormal IL-27/IL-27R expression to pregnancy complications such as spontaneous miscarriage, preeclampsia, and preterm birth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion and Conclusion</h3>\u0000 \u0000 <p>IL-27 plays a complex role at the maternal-fetal interface, with abnormal expression linked to several pregnancy complications. These findings highlight the need for further research to elucidate IL-27's mechanisms and develop targeted interventions. Future studies should aim to develop targeted interventions and improve therapeutic strategies for managing pregnancy complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Can Ozan Ulusoy, Ahmet Kurt, Zeynep Seyhanli, Burak Hizli, Mevlut Bucak, Recep Taha Agaoglu, Yüksel Oguz, Kadriye Yakut Yucel
Objectives
This study evaluates the association of novel inflammatory markers and Doppler parameters in late-onset FGR (fetal growth restriction), utilizing a machine-learning approach to enhance predictive accuracy.
Materials and Methods
A retrospective case–control study was conducted at the Department of Perinatology, Ministry of Health Etlik City Hospital, Ankara, from 2023 to 2024. The study included 240 patients between 32 and 37 weeks of gestation, divided equally between patients diagnosed with late-onset FGR and a control group. We focused on novel inflammatory markers—systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), and neutrophil-percentage-to-albumin ratio (NPAR)—and their correlation with Doppler parameters of umbilical and uterine arteries. Machine-learning algorithms were employed to analyze the data collected, including demographic, neonatal, and clinical parameters, to develop a predictive model for FGR.
Results
The machine-learning model, specifically the Random Forest algorithm, effectively integrated the inflammatory markers with Doppler parameters to predict FGR. NPAR showed a significant correlation with FGR presence, providing a robust tool in the predictive model (Accuracy 77%, area under the curve [AUC] 0.851). In contrast, SII and SIRI, while useful, did not achieve the same level of predictive accuracy (Accuracy 75% AUC 0.818 and Accuracy 73% AUC 0.793, respectively). The model highlighted the potential of combining ultrasound measurements with inflammatory markers to improve diagnostic accuracy for late-onset FGR.
Conclusions
This study illustrates the efficacy of integrating machines with traditional diagnostic methods to enhance the prediction of late-onset FGR. Further research with a larger cohort is recommended to validate these findings and refine the predictive model, which could lead to improved clinical outcomes for affected pregnancies.
{"title":"Role of Inflammatory Markers and Doppler Parameters in Late-Onset Fetal Growth Restriction: A Machine-Learning Approach","authors":"Can Ozan Ulusoy, Ahmet Kurt, Zeynep Seyhanli, Burak Hizli, Mevlut Bucak, Recep Taha Agaoglu, Yüksel Oguz, Kadriye Yakut Yucel","doi":"10.1111/aji.70004","DOIUrl":"https://doi.org/10.1111/aji.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study evaluates the association of novel inflammatory markers and Doppler parameters in late-onset FGR (fetal growth restriction), utilizing a machine-learning approach to enhance predictive accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A retrospective case–control study was conducted at the Department of Perinatology, Ministry of Health Etlik City Hospital, Ankara, from 2023 to 2024. The study included 240 patients between 32 and 37 weeks of gestation, divided equally between patients diagnosed with late-onset FGR and a control group. We focused on novel inflammatory markers—systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), and neutrophil-percentage-to-albumin ratio (NPAR)—and their correlation with Doppler parameters of umbilical and uterine arteries. Machine-learning algorithms were employed to analyze the data collected, including demographic, neonatal, and clinical parameters, to develop a predictive model for FGR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The machine-learning model, specifically the Random Forest algorithm, effectively integrated the inflammatory markers with Doppler parameters to predict FGR. NPAR showed a significant correlation with FGR presence, providing a robust tool in the predictive model (Accuracy 77%, area under the curve [AUC] 0.851). In contrast, SII and SIRI, while useful, did not achieve the same level of predictive accuracy (Accuracy 75% AUC 0.818 and Accuracy 73% AUC 0.793, respectively). The model highlighted the potential of combining ultrasound measurements with inflammatory markers to improve diagnostic accuracy for late-onset FGR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study illustrates the efficacy of integrating machines with traditional diagnostic methods to enhance the prediction of late-onset FGR. Further research with a larger cohort is recommended to validate these findings and refine the predictive model, which could lead to improved clinical outcomes for affected pregnancies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT06372938</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna M. Powell, Jessica Weng, Brittany R. Jones, Lauren Hesse, Ann Johnson, Elizabeth A. Bonney, Indira U. Mysorekar
{"title":"Empowering Reproductive Healthcare: Reflections and Calls to Action From the 2024 American Society of Reproductive Immunology (ASRI) Meeting Policy Advocacy Session","authors":"Anna M. Powell, Jessica Weng, Brittany R. Jones, Lauren Hesse, Ann Johnson, Elizabeth A. Bonney, Indira U. Mysorekar","doi":"10.1111/aji.13943","DOIUrl":"https://doi.org/10.1111/aji.13943","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Teresa Chou, Karolina J. Senkow, Megan B. Nguyen, Payal V. Patel, Kirtana Sandepudi, Lee A. Cooper, Jeffery A. Goldstein
Problem
The placental membranes are a key barrier to fetal and uterine infection. Inflammation of the membranes, diagnosed as maternal inflammatory response (MIR) or alternatively as acute chorioamnionitis, is associated with adverse maternal-fetal outcomes. MIR is staged 1–3, with higher stages indicating more hazardous inflammation. However, the diagnosis relies upon subjective evaluation and has not been deeply characterized. The goal of this work is to develop a cell classifier for eight placental membrane cells and quantitatively characterize MIR1–2.
Method of Study
Hematoxylin and eosin (H&E)-stained placental membrane slides were digitized. A convolutional neural network was trained on a dataset of hand-annotated and machine learning-identified cells. Overall cell class-level metrics were calculated. The model was applied to 20 control, 20 MIR1, and 23 MIR2 placental membrane cases. MIR cell composition and neutrophil distribution were assessed via density and Ripley's cross K-function. Clinical data were compared to neutrophil density and distribution.
Results
The classification model achieved a test-set accuracy of 0.845, with high precision and recall for amniocytes, decidual cells, endothelial cells, and trophoblasts. Using this model to classify 53 073 cells from healthy and MIR1–2 placental membranes, we found that (1) MIR1–2 have higher neutrophil density and fewer decidual cells and trophoblasts, (2) Neutrophils colocalize heavily around decidual cells in healthy placental membranes and around trophoblasts in MIR1, (3) Neutrophil density impacts distribution in MIR, and (4) Neutrophil metrics correlate with features of clinical chorioamnionitis.
Conclusions
This paper introduces cell classification into the placental membranes and quantifies cell composition and neutrophil spatial distributions in MIR.
{"title":"Quantitative Modeling to Characterize Maternal Inflammatory Response of Histologic Chorioamnionitis in Placental Membranes","authors":"Teresa Chou, Karolina J. Senkow, Megan B. Nguyen, Payal V. Patel, Kirtana Sandepudi, Lee A. Cooper, Jeffery A. Goldstein","doi":"10.1111/aji.13944","DOIUrl":"https://doi.org/10.1111/aji.13944","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>The placental membranes are a key barrier to fetal and uterine infection. Inflammation of the membranes, diagnosed as maternal inflammatory response (MIR) or alternatively as acute chorioamnionitis, is associated with adverse maternal-fetal outcomes. MIR is staged 1–3, with higher stages indicating more hazardous inflammation. However, the diagnosis relies upon subjective evaluation and has not been deeply characterized. The goal of this work is to develop a cell classifier for eight placental membrane cells and quantitatively characterize MIR1–2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Hematoxylin and eosin (H&E)-stained placental membrane slides were digitized. A convolutional neural network was trained on a dataset of hand-annotated and machine learning-identified cells. Overall cell class-level metrics were calculated. The model was applied to 20 control, 20 MIR1, and 23 MIR2 placental membrane cases. MIR cell composition and neutrophil distribution were assessed via density and Ripley's cross <i>K</i>-function. Clinical data were compared to neutrophil density and distribution.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The classification model achieved a test-set accuracy of 0.845, with high precision and recall for amniocytes, decidual cells, endothelial cells, and trophoblasts. Using this model to classify 53 073 cells from healthy and MIR1–2 placental membranes, we found that (1) MIR1–2 have higher neutrophil density and fewer decidual cells and trophoblasts, (2) Neutrophils colocalize heavily around decidual cells in healthy placental membranes and around trophoblasts in MIR1, (3) Neutrophil density impacts distribution in MIR, and (4) Neutrophil metrics correlate with features of clinical chorioamnionitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This paper introduces cell classification into the placental membranes and quantifies cell composition and neutrophil spatial distributions in MIR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Uterine contractions signal labor onset, with elevated pro-inflammatory cytokines playing a pivotal role. Prior studies have explored their effects on prostaglandins, oxytocin, and signaling pathways, but have overlooked their direct effects on uterine contractions. Here, we aim to investigate the direct effects of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) on contractions to ascertain if they have immediate observable effects like those reported for lipopolysaccharide (LPS) and other effects.
Method of Study
Tension recordings were used to assess the direct effects of cytokines and/or LPS on mouse uterine contractions. Calcium imaging was employed to observe calcium oscillations in cytokine-pretreated myometrial smooth muscle cells (MSMCs) in response to oxytocin. The release of inflammatory cytokines and chemokines from uterine explants after LPS and/or cytokines application was investigated using Luminex.
Results
IL-1β, IL-6, and TNF-α rapidly enhanced contractions of term pregnant mouse uterus. LPS combined with TNF-α intensified contractions compared to LPS alone, although this effect was not statistically significant in our results (p > 0.050). Pretreatment of MSMCs with IL-1β, IL-6, or TNF-α increased calcium oscillations in response to oxytocin. LPS and/or cytokine significantly stimulated the release of IL-1β, IL-6, TNF-α, Chemokine (C-X-C motif) ligand 1 (CXCL1), and monocyte chemoattractant protein-1 (MCP1) from uterine explants in vitro.
Conclusions
Inflammatory cytokines have short-term and long-term effects on mouse uterine contractions, which together contribute to progressively stronger contractions during labor.
{"title":"Direct Effects of Inflammatory Cytokines on Mouse Uterine Contraction","authors":"Junjie Bao, Caihan Zhao, Xiaodi Wang, Shiyun Liu, Lele Wang, Yong Zou, Huishu Liu","doi":"10.1111/aji.13938","DOIUrl":"https://doi.org/10.1111/aji.13938","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Uterine contractions signal labor onset, with elevated pro-inflammatory cytokines playing a pivotal role. Prior studies have explored their effects on prostaglandins, oxytocin, and signaling pathways, but have overlooked their direct effects on uterine contractions. Here, we aim to investigate the direct effects of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) on contractions to ascertain if they have immediate observable effects like those reported for lipopolysaccharide (LPS) and other effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Tension recordings were used to assess the direct effects of cytokines and/or LPS on mouse uterine contractions. Calcium imaging was employed to observe calcium oscillations in cytokine-pretreated myometrial smooth muscle cells (MSMCs) in response to oxytocin. The release of inflammatory cytokines and chemokines from uterine explants after LPS and/or cytokines application was investigated using Luminex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IL-1β, IL-6, and TNF-α rapidly enhanced contractions of term pregnant mouse uterus. LPS combined with TNF-α intensified contractions compared to LPS alone, although this effect was not statistically significant in our results (<i>p</i> > 0.050). Pretreatment of MSMCs with IL-1β, IL-6, or TNF-α increased calcium oscillations in response to oxytocin. LPS and/or cytokine significantly stimulated the release of IL-1β, IL-6, TNF-α, Chemokine (C-X-C motif) ligand 1 (CXCL1), and monocyte chemoattractant protein-1 (MCP1) from uterine explants in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Inflammatory cytokines have short-term and long-term effects on mouse uterine contractions, which together contribute to progressively stronger contractions during labor.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irene Monticciolo, Alice Guarano, Annalisa Inversetti, Greta Barbaro, Nicoletta Di Simone
Problem
Recurrent pregnancy loss (RPL) is defined as the failure of two or more pregnancies and affects approximately 5% of couples, often without a clear cause. The etiologies of RPL include factors such as maternal age, endocrine dysfunction, uterine abnormalities, chromosomal abnormalities, thrombophilias, infections, and autoimmune disorders. However, these conditions account for only 50%–60% of RPL cases. Research has explored whether an altered immune system, compared to the physiological state, may be linked to RPL. This review aims to determine whether specific immunophenotypes are associated with unexplained Recurrent Pregnancy Loss (uRPL) and whether targeted therapies addressing specific immunophenotypic alterations can improve pregnancy outcomes.
Methods
A literature review was conducted using Pubmed/Medline, Scopus, and Embase databases, analyzing data from 95 articles published between 2001 and 2023. The roles of various cells of the immune system (B lymphocytes, T lymphocytes, natural killer cells, macrophages) in different tissues (peripheral blood, menstrual blood) were specifically investigated in women with uRPL.
Discussion and Conclusion
Specific immunophenotypes have been demonstrated to be associated with this condition. However, there is a need to standardize immunophenotyping assays and conduct more trials to stratify RPL risk and improve potential therapeutic strategies.
{"title":"Unexplained Recurrent Pregnancy Loss: Clinical Application of Immunophenotyping","authors":"Irene Monticciolo, Alice Guarano, Annalisa Inversetti, Greta Barbaro, Nicoletta Di Simone","doi":"10.1111/aji.13939","DOIUrl":"10.1111/aji.13939","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Recurrent pregnancy loss (RPL) is defined as the failure of two or more pregnancies and affects approximately 5% of couples, often without a clear cause. The etiologies of RPL include factors such as maternal age, endocrine dysfunction, uterine abnormalities, chromosomal abnormalities, thrombophilias, infections, and autoimmune disorders. However, these conditions account for only 50%–60% of RPL cases. Research has explored whether an altered immune system, compared to the physiological state, may be linked to RPL. This review aims to determine whether specific immunophenotypes are associated with unexplained Recurrent Pregnancy Loss (uRPL) and whether targeted therapies addressing specific immunophenotypic alterations can improve pregnancy outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A literature review was conducted using Pubmed/Medline, Scopus, and Embase databases, analyzing data from 95 articles published between 2001 and 2023. The roles of various cells of the immune system (B lymphocytes, T lymphocytes, natural killer cells, macrophages) in different tissues (peripheral blood, menstrual blood) were specifically investigated in women with uRPL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion and Conclusion</h3>\u0000 \u0000 <p>Specific immunophenotypes have been demonstrated to be associated with this condition. However, there is a need to standardize immunophenotyping assays and conduct more trials to stratify RPL risk and improve potential therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SARS-CoV-2 infection during pregnancy has severe consequences on maternal and neonatal health. Presently, vaccination stands as a critical preventive measure for mitigating infection-related risks. Although the initial clinical trials for the COVID-19 vaccines excluded pregnant women, subsequent investigations have indicated mRNA vaccinations' effectiveness and short-term safety during pregnancy. However, there is a lack of information regarding the potential biodistribution of the vaccine mRNA during pregnancy and lactation. Recent findings indicate that COVID-19 vaccine mRNA has been detected in breast milk, suggesting that its presence is not confined to the injection site and raises the possibility of similar distribution to the placenta and the fetus. Furthermore, the potential effects and responses of the placenta and fetus to the vaccine mRNA are still unknown. While potential risks might exist with the exposure of the placenta and fetus to the COVID-19 mRNA vaccine, the application of mRNA therapies for maternal and fetal conditions offers a groundbreaking prospect. Future research should leverage the unique opportunity provided by the first-ever application of mRNA vaccines in humans to understand their biodistribution and impact on the placenta and fetus in pregnant women. Such insights could substantially advance the development of safer and more effective future mRNA-based therapies during pregnancy.
{"title":"COVID-19 Vaccine mRNA Biodistribution: Maternal and Fetal Exposure Risks","authors":"Connie Zhong, Koral Cohen, Xinhua Lin, Emily Schiller, Surendra Sharma, Nazeeh Hanna","doi":"10.1111/aji.13934","DOIUrl":"10.1111/aji.13934","url":null,"abstract":"<div>\u0000 \u0000 <p>SARS-CoV-2 infection during pregnancy has severe consequences on maternal and neonatal health. Presently, vaccination stands as a critical preventive measure for mitigating infection-related risks. Although the initial clinical trials for the COVID-19 vaccines excluded pregnant women, subsequent investigations have indicated mRNA vaccinations' effectiveness and short-term safety during pregnancy. However, there is a lack of information regarding the potential biodistribution of the vaccine mRNA during pregnancy and lactation. Recent findings indicate that COVID-19 vaccine mRNA has been detected in breast milk, suggesting that its presence is not confined to the injection site and raises the possibility of similar distribution to the placenta and the fetus. Furthermore, the potential effects and responses of the placenta and fetus to the vaccine mRNA are still unknown. While potential risks might exist with the exposure of the placenta and fetus to the COVID-19 mRNA vaccine, the application of mRNA therapies for maternal and fetal conditions offers a groundbreaking prospect. Future research should leverage the unique opportunity provided by the first-ever application of mRNA vaccines in humans to understand their biodistribution and impact on the placenta and fetus in pregnant women. Such insights could substantially advance the development of safer and more effective future mRNA-based therapies during pregnancy.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aims to evaluate the correlation between anti-annexin A5 (aANXA5) antibody in the blood and pregnancy outcomes .
Methods
This study is a retrospective cohort study based on singleton pregnancies of the Third Affiliated Hospital of Wenzhou Medical University from May 2018 to December 2022. Baseline characteristics were collected from all participants. Logistic regression and interaction effect analyses were utilized to examine the risk impact of aANXA5 on pregnancy complications, adjusting for age, BMI, abortion, ANA, and aCL. Restricted cubic spline (RCS) and threshold effect analysis were applied to explore the relationship between aANXA5 levels and preterm birth (PTB), as well as pregnancy-induced hypertension (PIH).
Results
The study included 501 participants, with 51 (10.2%) testing positive for aANXA5 and 450 (89.8%) testing negative. The aANXA5 positive group exhibited higher rates of ANA and antibodies to thyroglobulin (TGAb), along with increased incidences of PTB and PIH. Positive aANXA5 status was independently linked to an elevated risk of PTB (OR: 2.53, 95% CI: 1.30–4.94) and PIH (OR: 4.23, 95% CI: 1.54–11.62). Subsequent subgroup analysis indicated no significant interaction between the groups (p > 0.05). Threshold analysis revealed that the OR for PTB was 1.20 (95% CI: 1.03–1.39) in participants with aANXA5 levels ≥ 32.77 ng/mL, and the OR for PIH was 1.62 (95% CI: 1.15–2.28) in those with aANXA5 levels ≥ 33.20 ng/mL.
Conclusion
AANXA5 is independently associated with an increased risk of PTB and PIH. The identified optimal predictive cutoff values are 32.77 ng/mL for PTB and 33.20 ng/mL for PIH.
{"title":"Association of Anti-Annexin A5 Antibody With Pregnancy Outcomes: A Cohort Study","authors":"Xueke Guo, Junmiao Xiang, Wenmei Zhang, Xiuying Zheng, Yuanyuan Dai, Zhuhua Cai","doi":"10.1111/aji.13936","DOIUrl":"10.1111/aji.13936","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to evaluate the correlation between anti-annexin A5 (aANXA5) antibody in the blood and pregnancy outcomes\u0000.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study is a retrospective cohort study based on singleton pregnancies of the Third Affiliated Hospital of Wenzhou Medical University from May 2018 to December 2022. Baseline characteristics were collected from all participants. Logistic regression and interaction effect analyses were utilized to examine the risk impact of aANXA5 on pregnancy complications, adjusting for age, BMI, abortion, ANA, and aCL. Restricted cubic spline (RCS) and threshold effect analysis were applied to explore the relationship between aANXA5 levels and preterm birth (PTB), as well as pregnancy-induced hypertension (PIH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 501 participants, with 51 (10.2%) testing positive for aANXA5 and 450 (89.8%) testing negative. The aANXA5 positive group exhibited higher rates of ANA and antibodies to thyroglobulin (TGAb), along with increased incidences of PTB and PIH. Positive aANXA5 status was independently linked to an elevated risk of PTB (OR: 2.53, 95% CI: 1.30–4.94) and PIH (OR: 4.23, 95% CI: 1.54–11.62). Subsequent subgroup analysis indicated no significant interaction between the groups (<i>p</i> > 0.05). Threshold analysis revealed that the OR for PTB was 1.20 (95% CI: 1.03–1.39) in participants with aANXA5 levels ≥ 32.77 ng/mL, and the OR for PIH was 1.62 (95% CI: 1.15–2.28) in those with aANXA5 levels ≥ 33.20 ng/mL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>AANXA5 is independently associated with an increased risk of PTB and PIH. The identified optimal predictive cutoff values are 32.77 ng/mL for PTB and 33.20 ng/mL for PIH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.13936","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sadullah Özkan, Alperen Aksan, Dilara Kurt, Ahmet Kurt, Fahri B. Fıratlıgil, Serap Sucu, Sadun Sucu, Yıldız A. Reis, Burcu G. Öztürk, Ali T. Çağlar
Problem
This study aims to evaluate the effectiveness of inflammation indexes (systemic immune-inflammation index [SII], systemic inflammation response index [SIRI], pan-immune inflammation value [PIV], and neutrophil-to-lymphocyte ratio [NLR]) in the diagnosis of intrahepatic cholestasis of pregnancy (ICP).
Method of Study
A retrospective study was conducted, reviewing medical records of patients diagnosed with ICP who delivered between October 1, 2022, and May 31, 2023, at the Perinatology clinic of Etlik City Hospital, Ankara. A control group of healthy pregnant women with uncomplicated pregnancies was also included. Demographic data, clinical characteristics, and laboratory results, including systemic inflammation indices and liver enzyme levels, were collected and analyzed.
Results
A total of 242 participants were included, with 121 ICP patients and 121 controls. White blood cell count, neutrophil count, and monocyte count showed significant differences between the two groups (p = 0.011, p = 0.004, and p = 0.039, respectively). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly elevated in the ICP group (p < 0.001 for both). SII and NLR were higher in the ICP group compared to controls (p = 0.032 and p = 0.010, respectively). Receiver operating characteristic (ROC) analysis revealed moderate predictive values for SII (area under the curve [AUC] = 0.581, p = 0.030) and NLR (AUC = 0.598, p = 0.009), with no significant difference in their predictive power (p = 0.502).
Conclusions
Systemic inflammation indices such as SII and NLR offer a cost-effective and rapid means of diagnosing ICP, potentially complementing or surpassing traditional biomarkers like bile acid levels and liver function tests (LFTs). These indices can be easily integrated into routine clinical practice, providing timely intervention to improve maternal and fetal outcomes. Further research is warranted to confirm these findings and establish standardized protocols for their use in ICP management.
{"title":"Are Systemic Inflammation Markers Reliable for Diagnosing Intrahepatic Cholestasis of Pregnancy? A Retrospective Cohort Study","authors":"Sadullah Özkan, Alperen Aksan, Dilara Kurt, Ahmet Kurt, Fahri B. Fıratlıgil, Serap Sucu, Sadun Sucu, Yıldız A. Reis, Burcu G. Öztürk, Ali T. Çağlar","doi":"10.1111/aji.13937","DOIUrl":"10.1111/aji.13937","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>This study aims to evaluate the effectiveness of inflammation indexes (systemic immune-inflammation index [SII], systemic inflammation response index [SIRI], pan-immune inflammation value [PIV], and neutrophil-to-lymphocyte ratio [NLR]) in the diagnosis of intrahepatic cholestasis of pregnancy (ICP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>A retrospective study was conducted, reviewing medical records of patients diagnosed with ICP who delivered between October 1, 2022, and May 31, 2023, at the Perinatology clinic of Etlik City Hospital, Ankara. A control group of healthy pregnant women with uncomplicated pregnancies was also included. Demographic data, clinical characteristics, and laboratory results, including systemic inflammation indices and liver enzyme levels, were collected and analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 242 participants were included, with 121 ICP patients and 121 controls. White blood cell count, neutrophil count, and monocyte count showed significant differences between the two groups (<i>p</i> = 0.011, <i>p</i> = 0.004, and <i>p</i> = 0.039, respectively). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly elevated in the ICP group (<i>p</i> < 0.001 for both). SII and NLR were higher in the ICP group compared to controls (<i>p</i> = 0.032 and <i>p</i> = 0.010, respectively). Receiver operating characteristic (ROC) analysis revealed moderate predictive values for SII (area under the curve [AUC] = 0.581, <i>p</i> = 0.030) and NLR (AUC = 0.598, <i>p</i> = 0.009), with no significant difference in their predictive power (<i>p</i> = 0.502).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Systemic inflammation indices such as SII and NLR offer a cost-effective and rapid means of diagnosing ICP, potentially complementing or surpassing traditional biomarkers like bile acid levels and liver function tests (LFTs). These indices can be easily integrated into routine clinical practice, providing timely intervention to improve maternal and fetal outcomes. Further research is warranted to confirm these findings and establish standardized protocols for their use in ICP management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ying Wang, Fenyong Sun, Han Wu, Chaoyan Yue, Qiuhong Man
Purpose
Previous studies have identified associations between immune cell traits and endometriosis, but the causality of these relationships remains uncertain. In this study, we utilized Mendelian randomization (MR) to investigate the causal relationship between immune cell traits and endometriosis for the first time.
Methods
Seven hundred and thirty-one immune cell signatures associated with single-nucleotide polymorphisms (SNPs) were extracted from a published genome-wide association study (GWAS) involving 472 174 individuals, while endometriosis data, including four stages and seven subtypes, were obtained from the FinnGen consortium. Four methods were used for MR. The causal effect of immune cell traits on endometriosis was explored after Bonferroni correction.
Results
Significant causal relationship included 92 immune cell traits distributed among B cell (28 cells), cDC (2 cells), maturation stages of T cell (10 cells), monocyte (12 cells), Myeloid cell (5 cells), TBNK (13 cells), and Treg panels (22 cells). One of the most significant findings is that for every 1-standard deviation (SD) increase in CD8 on Central Memory CD8+ T cell, the risks of developing endometriosis of the fallopian tube increased by 72%. In the reverse MR analysis, a one-unit increase in the log odds of endometriosis of the ovary risk corresponded to a decrease in the absolute count of CD4+ CD8dim T cell by 0.10.
Conclusion
This study represents the first comprehensive evaluation of the causal effects of immune cell traits on the risk/protection of different stages/subtypes of endometriosis. The findings highlight the complex and significant role of immune-derived factors in the pathogenesis of the disease.
{"title":"Bidirectional Mendelian Randomization Reveals Causal Effects of Immune Cell Traits on Endometriosis Risk","authors":"Ying Wang, Fenyong Sun, Han Wu, Chaoyan Yue, Qiuhong Man","doi":"10.1111/aji.13917","DOIUrl":"10.1111/aji.13917","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Previous studies have identified associations between immune cell traits and endometriosis, but the causality of these relationships remains uncertain. In this study, we utilized Mendelian randomization (MR) to investigate the causal relationship between immune cell traits and endometriosis for the first time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Seven hundred and thirty-one immune cell signatures associated with single-nucleotide polymorphisms (SNPs) were extracted from a published genome-wide association study (GWAS) involving 472 174 individuals, while endometriosis data, including four stages and seven subtypes, were obtained from the FinnGen consortium. Four methods were used for MR. The causal effect of immune cell traits on endometriosis was explored after Bonferroni correction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant causal relationship included 92 immune cell traits distributed among B cell (28 cells), cDC (2 cells), maturation stages of T cell (10 cells), monocyte (12 cells), Myeloid cell (5 cells), TBNK (13 cells), and Treg panels (22 cells). One of the most significant findings is that for every 1-standard deviation (SD) increase in CD8 on Central Memory CD8<sup>+</sup> T cell, the risks of developing endometriosis of the fallopian tube increased by 72%. In the reverse MR analysis, a one-unit increase in the log odds of endometriosis of the ovary risk corresponded to a decrease in the absolute count of CD4<sup>+</sup> CD8<sup>dim</sup> T cell by 0.10.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study represents the first comprehensive evaluation of the causal effects of immune cell traits on the risk/protection of different stages/subtypes of endometriosis. The findings highlight the complex and significant role of immune-derived factors in the pathogenesis of the disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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