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Neonatal SARS-CoV-2 mRNA Vaccination Efficacy Is Influenced by Maternal Antibodies 新生儿 SARS-CoV-2 mRNA 疫苗接种效果受母体抗体影响
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-22 DOI: 10.1111/aji.70001
Amy Schumer, Elizabeth A. Bonney, Ethan Harby, Devdoot Majumdar

Problem

Vaccination in pregnancy guards against infection. Maternal antibodies, however, can inhibit antibody production in neonates. We sought to determine the effects of maternal vaccination on neonatal immune response to a SARS-CoV-2 mRNA vaccine.

Method of Study

We hypothesized that mRNA-lipid nanoparticles (LNP) vaccination allows for a de novo neonatal antibody response even in the presence of vertically transmitted maternal antibodies. Female mice were vaccinated with SARS-CoV-2 spike receptor binding domain (RBD) mRNA-LNPs. Mice were then bred, and 21-day-old pups were inoculated with the same mRNA-LNPs. Spike-specific IgG ELISAs were performed using mouse serum. A SARS-CoV-2 spike protein peptide library to perform peptide ELISAs characterized high affinity binding domains within the spike protein. Results were analyzed with one-way ANOVAs with Tukey's multiple comparisons tests.

Results

Compared to pups of unvaccinated dams, there were high levels of spike-specific IgG detected in the pups of vaccinated dams at 3 weeks of life (p < 0.0001). After neonatal vaccination, pups of unvaccinated dams had higher spike-specific serum IgG than pups of vaccinated dams at 12 weeks of life (p < 0.001). Antibody specificity to peptide moieties within spike RBD were similar when comparing a vaccinated dam to her pup at Week 3 of life, with different binding affinities observed in the pups by Week 15 of life.

Conclusions

Pre-existing maternal antibodies may partially blunt the initial neonatal antibody response to mRNA-LNPs vaccination. This vaccine strategy, however, does not prohibit the subsequent development of a broad range of RBD antibody specificities that may be protective.

问题:孕期接种疫苗可预防感染。然而,母体抗体会抑制新生儿抗体的产生。我们试图确定母体接种 SARS-CoV-2 mRNA 疫苗对新生儿免疫反应的影响:我们假设,即使存在垂直传播的母源抗体,mRNA-脂质纳米颗粒(LNP)疫苗接种也能使新生儿产生新的抗体反应。雌性小鼠接种了 SARS-CoV-2 穗状受体结合域(RBD)mRNA-LNPs 疫苗。然后繁殖小鼠,并用相同的 mRNA-LNPs 接种 21 天大的幼鼠。使用小鼠血清进行尖峰特异性 IgG ELISA 检测。利用 SARS-CoV-2 穗状病毒蛋白肽库进行肽 ELISA,以确定穗状病毒蛋白中的高亲和力结合域。结果用单向方差分析和Tukey多重比较检验进行分析:与未接种疫苗的母鼠的幼崽相比,接种疫苗的母鼠的幼崽在出生 3 周时检测到了高水平的穗状病毒特异性 IgG(p < 0.0001)。新生儿接种疫苗后,未接种疫苗的母鼠的幼崽在出生后 12 周的血清穗状病毒特异性 IgG 高于接种疫苗的母鼠的幼崽(p < 0.001)。接种过疫苗的母鼠与出生后第3周的幼鼠相比,抗体对穗状病毒RBD中多肽分子的特异性相似,但在出生后第15周时,幼鼠与抗体的结合亲和力不同:结论:先前存在的母源抗体可能会部分削弱新生儿对 mRNA-LNPs 疫苗接种的初始抗体反应。然而,这种疫苗策略并不妨碍随后产生可能具有保护作用的多种 RBD 抗体特异性。
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引用次数: 0
Association Between Maternal Cytomegalovirus Seropositivity, Preterm Birth, and Preeclampsia in Two Cohorts From Quebec, Canada: A Mediation Analysis 加拿大魁北克两个群体中母体巨细胞病毒血清阳性、早产和先兆子痫之间的关系:中介分析
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-22 DOI: 10.1111/aji.13941
Safari Joseph Balegamire, Benoît Mâsse, François Audibert, Valerie Lamarre, Yves Giguere, Jean-Claude Forest, Isabelle Boucoiran

Problem

Preterm birth and preeclampsia significantly contribute to infant morbidity and mortality, posing critical public health concerns. Viral infections, particularly Cytomegalovirus (CMV), associated with chronic inflammation, may play a role in these adverse pregnancy outcomes. The contribution of CMV to preterm birth and preeclampsia requires further investigation.

Method of Study

Data from 6048 pregnant women from two prospective Quebec cohorts, recruited between May 2005 and August 2012, were analyzed. First-trimester CMV serology was the exposure variable. Associations were assessed using multivariable logistic regression adjusted by inverse probability treatment weighting (IPTW) of propensity scores. Mediation analyses estimated the direct effect of maternal CMV serostatus on preterm birth, excluding mediation by preeclampsia.

Results

Preterm birth and preeclampsia proportions were 5.1% (95% CI: 4.6–5.7) and 1.9% (95% CI: 1.6–2.3), respectively. Multivariable logistic regression adjusted by IPTW showed associations between CMV seropositivity and preterm birth (OR 1.20, 95% CI: 1.02–1.41) and CMV seropositivity and preeclampsia (OR 1.41, 95% CI: 1.08–1.84). Mediation analysis indicated that 97% of the total effect of CMV seropositivity on preterm birth is direct, with the remaining 3% mediated by preeclampsia.

Conclusions

CMV seropositivity appears to be a risk factor for both preterm birth and preeclampsia. The effect of maternal CMV seropositivity on preterm birth is primarily direct, not mediated by preeclampsia. Future studies should explore the impact of preventive measures against CMV infection on the incidence of preterm delivery and preeclampsia.

问题:早产和子痫前期是造成婴儿发病率和死亡率的重要原因,是公共卫生的重大问题。病毒感染,尤其是与慢性炎症相关的巨细胞病毒(CMV),可能是导致这些不良妊娠结局的原因之一。CMV对早产和子痫前期的影响需要进一步调查:分析了 2005 年 5 月至 2012 年 8 月间从魁北克两个前瞻性队列中招募的 6048 名孕妇的数据。首胎 CMV 血清学是暴露变量。使用多变量逻辑回归对相关性进行评估,并对倾向分数进行反概率治疗加权(IPTW)调整。中介分析估计了母体CMV血清状态对早产的直接影响,排除了先兆子痫的中介作用:早产和子痫前期的比例分别为 5.1%(95% CI:4.6-5.7)和 1.9%(95% CI:1.6-2.3)。经IPTW调整的多变量逻辑回归显示,CMV血清阳性与早产(OR 1.20,95% CI:1.02-1.41)和CMV血清阳性与子痫前期(OR 1.41,95% CI:1.08-1.84)之间存在关联。中介分析表明,CMV血清阳性对早产的总影响中有97%是直接影响,其余3%由子痫前期中介:CMV血清阳性似乎是早产和子痫前期的风险因素。结论:CMV血清阳性似乎是早产和先兆子痫的风险因素,母体CMV血清阳性对早产的影响主要是直接的,而不是由先兆子痫介导的。未来的研究应探讨 CMV 感染预防措施对早产和子痫前期发生率的影响。
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引用次数: 0
Hypertension and Cognitive Dysfunction in a Pregnant Rat Model of PE; a Role for CD4+ T Cells 妊娠大鼠 PE 模型中的高血压和认知功能障碍;CD4+ T 细胞的作用
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-20 DOI: 10.1111/aji.13935
Evangeline Deer, Owen Herrock, Kimberly Simmons, Nathan Campbell, Lorena Amaral, Baoying Zheng, Rachael Morris, Kedra Wallace, ELizabeth Hawthorne Cleveland, Sheila Belk, Cameronne Dodd, Babbette LaMarca
<div> <section> <h3> Objective</h3> <p>Preeclampsia (PE) is associated with hypertension (HTN) during pregnancy and activated CD4+ T cells, inflammatory cytokines, and autoantibodies to the angiotensin II type I receptor (AT1-AA). Having had COVID-19 (CV) during pregnancy is associated with an increased incidence of a PE-like phenotype. Both PE and CV have long-lasting neurological implications and studies show that nonpregnant COVID patients produce AT1-AA. We have shown that CD4+ T cells from PE women cause a PE phenotype in nude athymic rats. In this study, we sought to examine the role of CD4+ T cells from PE with a CV History (Hx) to contribute to a PE phenotype and to determine the importance of CD4+ T cells in cognitive dysfunction during pregnancy.</p> </section> <section> <h3> Methods</h3> <p>At delivery, blood and placentas were collected, and one million placental CD4+ T cells from each PE and each normotensive patient, with (NT) or without (NP) a CV (Hx) during pregnancy, were isolated, purified, and injected i.p. into a gestational day (GD) 12 pregnant nude athymic rat (one patient/rat). At GD19, blood pressure (MAP) and circulating factors were assessed in recipient rats. Cognitive function and memory were assessed using Novel Object Recognition and Barnes Maze tests, respectively. Placental ACE-2 activity and AT1-AA were measured from COVID Hx patients. A one- or two-way ANOVA with Bonferroni's multiple comparisons test was used for statistical analysis.</p> </section> <section> <h3> Results</h3> <p>Blood pressure was increased in patients with PE, with or without COVID, compared to NT patients. There were no significant changes in placental ACE activity in patients with COVID Hx with or without PE. AT1-AA was elevated in PE patients and in both PE and NT COVID Hx compared to control NP. In pregnant recipient rats, MAP increased in CV Hx PE (113 ± 2, <i>n</i> = 8) compared to CV Hx NT (101 ± 5, <i>n</i> = 6). PE and PE CV Hx CD4+ T Cell recipient rats exhibited impaired memory and cognitive dysfunction (<i>p</i> < 0.05), compared to control groups. Recipient rats of PE CV Hx CD4+ T cells had elevated AT1-AA compared to NT CV Hx recipients. Both COVID Hx groups and recipients of PE CD4+ T cells had elevated TNF alpha compared to NP.</p> </section> <section> <h3> Conclusion</h3> <p>Our findings indicate that pregnant patients with a Hx of COVID during pregnancy produce AT1-AA, with or without PE. Recipients of CD4+ T cells from PE with or without a CV Hx during pregnancy cause HTN and elevated AT1-AA. TNF-α is elevated in PE and in CV Hx NT and PE recipients. Interestingly, recipients of T cells from PE patients wi
目的 子痫前期(PE)与妊娠期高血压(HTN)、活化的 CD4+ T 细胞、炎症细胞因子和血管紧张素 II I 型受体(AT1-AA)自身抗体有关。妊娠期患 COVID-19 (CV)与 PE 类表型的发病率增加有关。PE 和 CV 都会对神经系统产生长期影响,研究表明,非妊娠 COVID 患者会产生 AT1-AA。我们已经证明,来自 PE 妇女的 CD4+ T 细胞会导致裸体无胸腺大鼠出现 PE 表型。在本研究中,我们试图研究有 CV 病史(Hx)的 PE 患者的 CD4+ T 细胞在导致 PE 表型中的作用,并确定 CD4+ T 细胞在妊娠期认知功能障碍中的重要性。 方法 在分娩时收集血液和胎盘,分离、纯化和注射一百万个来自每个 PE 和每个正常血压患者(妊娠期间有(NT)或无(NP)CV(Hx))的胎盘 CD4+ T 细胞到妊娠日(GD)12 的妊娠裸大鼠体内(每个患者/大鼠一只)。在 GD19 时,对受体大鼠的血压(MAP)和循环因子进行评估。认知功能和记忆分别通过新物体识别和巴恩斯迷宫测试进行评估。对 COVID Hx 患者的胎盘 ACE-2 活性和 AT1-AA 进行了测量。统计分析采用单因素或双因素方差分析,并进行 Bonferroni 多重比较检验。 结果 与 NT 患者相比,伴有或不伴有 COVID 的 PE 患者血压升高。无论是否患有 COVID,PE 患者的胎盘 ACE 活性均无明显变化。与对照 NP 相比,PE 患者以及 PE 和 NT COVID Hx 患者的 AT1-AA 均升高。在妊娠受体大鼠中,与CV Hx NT(101 ± 5,n = 6)相比,CV Hx PE(113 ± 2,n = 8)的MAP增加。与对照组相比,PE 和 PE CV Hx CD4+ T 细胞受体大鼠表现出记忆力减退和认知功能障碍(p < 0.05)。与NT CV Hx受体相比,PE CV Hx CD4+ T细胞受体大鼠的AT1-AA升高。与 NP 相比,COVID Hx 组和 PE CD4+ T 细胞受体的 TNF α 均升高。 结论 我们的研究结果表明,无论是否患有 PE,妊娠期患有 COVID 的孕妇都会产生 AT1-AA。无论是否在妊娠期间患过CVID,接受来自PE的CD4+T细胞都会导致高血压和AT1-AA升高。TNF-α在PE、CV Hx NT和PE受体中均升高。有趣的是,与 NP CD4+ T 细胞的受体大鼠相比,有或没有 CV Hx 的 PE 患者的 T 细胞受体在妊娠期间的认知功能更差。这些数据证明了 CD4+ T 细胞在高血压和 PE 期间神经功能受损中的重要性,无论是否在妊娠期间感染过 COVID-19。
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引用次数: 0
Analysis of the Predictive Factors for Chronic Endometritis Recurrence in Infertile Women 不孕妇女慢性子宫内膜炎复发的预测因素分析
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-18 DOI: 10.1111/aji.70002
Keisuke Shiobara, Keiji Kuroda, Shunsuke Ishiyama, Kazuki Nakao, Azusa Moriyama, Takashi Horikawa, Satoru Takamizawa, Shuko Nojiri, Koji Nakagawa, Rikikazu Sugiyama

Problem

To identify the predictive factors for the recurrence of chronic endometritis (CE) in infertile women.

Method of study

In this case-control study, 1170 infertile women recovered from CE and underwent fertility treatment between December 2018 and August 2021. Among the 146 women (12.5%) who did not conceive or experienced pregnancy loss in 18 months after CE recovery, 105 consecutive women who underwent repeat endometrial biopsy for CD138 immunostaining and endometrial bacterial culturing were recruited. Thereafter, patients with and without CE recurrence were compared.

Results

The total recurrence rate of CE was 29.5% (31 women). Multivariable logistic regression analysis to determine predictive factors for CE recurrence revealed that hysteroscopic surgery (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.02–0.56; p = 0.0009) and pregnancy loss (OR, 4.13; 95% CI, 1.31–13.05; p = 0.016) were significantly associated with decreased and increased CE recurrence rates, respectively. Also, reexamination with CD138 immunostaining after 16–18 months (OR, 9.75; 95% CI, 1.47–64.64; p = 0.024) was significantly associated with increased CE recurrence rates. Among 49 patients without a history of pregnancy loss, the cumulative CE recurrence rates after 6, 12, and 18 months were 5.6%, 13.5%, and 20.4%, respectively.

Conclusions

We recommend reexamination with endometrial CD138 immunostaining in patients with pregnancy loss or long-term infertility during fertility treatment. Hysteroscopic surgery without antibiotic therapy for CE associated with intrauterine abnormalities is also recommended.

问题 找出不孕妇女慢性子宫内膜炎(CE)复发的预测因素。 研究方法 在这项病例对照研究中,1170名不孕妇女在2018年12月至2021年8月期间从CE中康复并接受了生育治疗。在146名(12.5%)CE康复后18个月内未怀孕或出现妊娠失败的女性中,招募了105名连续接受重复子宫内膜活检以进行CD138免疫染色和子宫内膜细菌培养的女性。之后,对 CE 复发和未复发的患者进行比较。 结果 CE总复发率为29.5%(31名女性)。为确定 CE 复发的预测因素而进行的多变量逻辑回归分析表明,宫腔镜手术(几率比 [OR],0.10;95% 置信区间 [CI],0.02-0.56;P = 0.0009)和妊娠失败(OR,4.13;95% CI,1.31-13.05;P = 0.016)分别与 CE 复发率的降低和升高显著相关。此外,16-18 个月后再次进行 CD138 免疫染色检查(OR,9.75;95% CI,1.47-64.64;p = 0.024)与 CE 复发率的增加有明显相关性。在 49 名无妊娠失败史的患者中,6、12 和 18 个月后的 CE 复发率分别为 5.6%、13.5% 和 20.4%。 结论 我们建议在不孕治疗期间对妊娠失败或长期不孕患者进行子宫内膜 CD138 免疫染色复查。对于与宫内畸形相关的 CE,我们还建议进行宫腔镜手术,但无需抗生素治疗。
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引用次数: 0
Chlorophyll Derivatives Exert Greater Potency Over Progesterone in the Prevention of Infection-Induced Preterm Birth in Murine Models 叶绿素衍生物在小鼠模型中预防感染诱发的早产方面比黄体酮更有效
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-18 DOI: 10.1111/aji.70000
Adaeze P. Uchendu, Eric K. Omogbai, Philip A. Obarisiagbon, Uyi G. Omogiade, Enitome E. Bafor

Problem

Preterm birth (PTB) is a significant cause of maternal and neonatal morbidity and mortality worldwide. However, the effectiveness of progesterone (P4) which is clinically used for PTB management remains controversial and necessitates research into new therapeutic options

Method of Study

In the current study, we investigated the effectiveness of two chlorophyll derivatives, pheophorbide a (PBa) and pheophytin a (PTa), in counteracting PTB. Timed-pregnant mice (gestation day 17 ± 0.5) received lipopolysaccharide (LPS) (25 µg/mouse) or phosphate-buffered saline (PBS) intraperitoneally, with PBa, PTa, progesterone (P4), and co-administration of P4 and ibuprofen (IBP), administered orally 2 h prior.

Results

The LPS group experienced PTB and 100% fetal mortality, whereas the PBa and PTa groups showed a delayed onset of LPS-induced PTB, with significantly decreased PTB rate and fetal mortality. In addition, PBa and PTa suppressed LPS-induced pro-inflammatory cytokines and NF-κB transcription factor while increasing anti-inflammatory cytokines in the placenta and uterus.

Conclusions

Our findings indicate that the chlorophyll derivatives, PBa and PTa increase fetal survival in infection-induced PTB and demonstrate greater efficacy than P4 in preventing PTB.

问题 早产(PTB)是全球孕产妇和新生儿发病率和死亡率的一个重要原因。然而,临床上用于治疗早产的黄体酮(P4)的有效性仍存在争议,因此有必要研究新的治疗方案。 研究方法 在本研究中,我们探讨了两种叶绿素衍生物--叶绿素a(PBa)和叶绿素a(PTa)--对抗早产的有效性。定时妊娠小鼠(妊娠天数为 17 ± 0.5)腹腔注射脂多糖(LPS)(25 µg/只)或磷酸盐缓冲盐水(PBS),2 小时前口服 PBa、PTa、黄体酮(P4)或同时服用 P4 和布洛芬(IBP)。 结果 LPS 组出现 PTB,胎儿死亡率为 100%,而 PBa 和 PTa 组 LPS 诱导的 PTB 起病延迟,PTB 率和胎儿死亡率显著降低。此外,PBa 和 PTa 还能抑制 LPS 诱导的促炎细胞因子和 NF-κB 转录因子,同时增加胎盘和子宫中的抗炎细胞因子。 结论 我们的研究结果表明,叶绿素衍生物 PBa 和 PTa 能提高感染诱发的 PTB 的胎儿存活率,在预防 PTB 方面比 P4 更有效。
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引用次数: 0
Emerging Roles of IL-27 in Trophoblast Cells and Pregnancy Complications IL-27 在滋养层细胞和妊娠并发症中的新作用
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-18 DOI: 10.1111/aji.13942
Yi-Hua Luo, Yang-Yang Zhang, Ming-Qing Li, Xin-Yan Zhang, Zi-Meng Zheng

Problem

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.

问题 自然流产、子痫前期和早产等妊娠并发症持续存在,尽管目前旨在预防和治疗这些疾病的干预措施大多不成功。白细胞介素-27(IL-27)由 p28 和 EBI3 亚基组成,与 IL-27R 结合,后者由 gp130 和 IL-27Rα(也称为 WSX-1 或 TCCR)组成,在肿瘤发生和炎症调节中起着关键作用。在母胎界面,滋养层细胞、子宫内膜基质细胞和蜕膜细胞中都检测到了 IL-27 的表达。IL-27/IL-27R水平异常与不良妊娠结局有关,包括自然流产、子痫前期和早产。本综述旨在探讨 IL-27 在母胎界面的表达及其信号通路,揭示 IL-27 在妊娠并发症中的复杂作用。 研究方法 使用 PubMed/Medline、Scopus 和 Embase 数据库进行了全面的文献综述,分析了有关 IL-27 在母胎界面的表达及其信号通路的研究。综述的重点是确定各种细胞类型中是否存在 IL-27,并将 IL-27/IL-27R 的异常表达与自然流产、子痫前期和早产等妊娠并发症联系起来。 讨论与结论 IL-27 在母胎界面中扮演着复杂的角色,其异常表达与多种妊娠并发症有关。这些发现强调了进一步研究的必要性,以阐明 IL-27 的作用机制并开发有针对性的干预措施。未来的研究应致力于开发有针对性的干预措施,并改进治疗策略,以控制妊娠并发症。
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引用次数: 0
Role of Inflammatory Markers and Doppler Parameters in Late-Onset Fetal Growth Restriction: A Machine-Learning Approach 炎症标记物和多普勒参数在晚期胎儿生长受限中的作用:机器学习方法
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-18 DOI: 10.1111/aji.70004
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.

Trial Registration

ClinicalTrials.gov identifier: NCT06372938

目的 本研究利用机器学习方法提高预测的准确性,评估晚发 FGR(胎儿生长受限)中新型炎症标记物与多普勒参数的关联。 材料与方法 一项回顾性病例对照研究于 2023 年至 2024 年在安卡拉埃特里克市卫生部医院围产医学科进行。该研究包括 240 名妊娠 32 至 37 周的患者,诊断为晚发性 FGR 的患者和对照组各占一半。我们重点研究了新型炎症标记物--系统免疫炎症指数(SII)、系统炎症反应指数(SIRI)和中性粒细胞百分比与白蛋白比率(NPAR)--及其与脐动脉和子宫动脉多普勒参数的相关性。采用机器学习算法分析收集到的数据,包括人口统计学、新生儿和临床参数,以建立 FGR 的预测模型。 结果 机器学习模型,特别是随机森林算法,有效地整合了炎症标记物和多普勒参数来预测 FGR。NPAR 与 FGR 存在明显的相关性,为预测模型提供了强有力的工具(准确率 77%,曲线下面积 [AUC] 0.851)。相比之下,SII 和 SIRI 虽然有用,但预测准确率却没有达到同样的水平(准确率分别为 75% AUC 0.818 和 73% AUC 0.793)。该模型强调了将超声测量与炎症标志物相结合以提高晚发 FGR 诊断准确性的潜力。 结论 本研究说明了将机器与传统诊断方法相结合以提高晚发 FGR 预测的有效性。建议对更大的队列进行进一步研究,以验证这些发现并完善预测模型,从而改善受影响妊娠的临床结果。 试验注册 ClinicalTrials.gov identifier:NCT06372938
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引用次数: 0
Empowering Reproductive Healthcare: Reflections and Calls to Action From the 2024 American Society of Reproductive Immunology (ASRI) Meeting Policy Advocacy Session 增强生殖保健能力:2024 年美国生殖免疫学会 (ASRI) 会议政策宣传会议的思考和行动呼吁
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-16 DOI: 10.1111/aji.13943
Anna M. Powell, Jessica Weng, Brittany R. Jones, Lauren Hesse, Ann Johnson, Elizabeth A. Bonney, Indira U. Mysorekar
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引用次数: 0
Quantitative Modeling to Characterize Maternal Inflammatory Response of Histologic Chorioamnionitis in Placental Membranes 用定量模型描述胎膜组织学绒毛膜羊膜炎的母体炎症反应
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-16 DOI: 10.1111/aji.13944
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.

问题 胎膜是胎儿和子宫感染的关键屏障。胎膜炎症可诊断为产妇炎症反应(MIR)或急性绒毛膜羊膜炎,与不良的母胎结局有关。MIR 可分为 1-3 级,级别越高,炎症越严重。然而,该诊断依赖于主观评价,尚未深入研究其特征。这项工作的目的是为八种胎盘膜细胞开发一种细胞分类器,并定量描述 MIR1-2 的特征。 研究方法 对经血沉和伊红(H&E)染色的胎盘膜切片进行数字化处理。在手工标注和机器学习识别的细胞数据集上训练卷积神经网络。计算了整体细胞类级指标。该模型适用于 20 个对照组、20 个 MIR1 和 23 个 MIR2 胎盘膜病例。通过密度和 Ripley's 交叉 K 函数评估 MIR 细胞组成和中性粒细胞分布。将临床数据与中性粒细胞密度和分布进行比较。 结果 该分类模型的测试集准确率为 0.845,对羊膜细胞、蜕膜细胞、内皮细胞和滋养层细胞的准确率和召回率都很高。使用该模型对来自健康胎盘和 MIR1-2 胎盘膜的 53 073 个细胞进行分类,我们发现:(1) MIR1-2 中性粒细胞密度较高,蜕膜细胞和滋养层细胞较少、(2)中性粒细胞在健康胎盘膜的蜕膜细胞周围大量聚集,而在 MIR1 中则聚集在滋养层细胞周围;(3)中性粒细胞密度影响 MIR 的分布;(4)中性粒细胞指标与临床绒毛膜羊膜炎的特征相关。 结论 本文将细胞分类引入胎盘膜,并量化了细胞组成和中性粒细胞在 MIR 中的空间分布。
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引用次数: 0
Direct Effects of Inflammatory Cytokines on Mouse Uterine Contraction 炎症细胞因子对小鼠子宫收缩的直接影响
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-15 DOI: 10.1111/aji.13938
Junjie Bao, Caihan Zhao, Xiaodi Wang, Shiyun Liu, Lele Wang, Yong Zou, Huishu Liu

Problem

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.

问题 子宫收缩是分娩开始的信号,而促炎细胞因子的升高起着关键作用。先前的研究探讨了它们对前列腺素、催产素和信号通路的影响,但忽略了它们对子宫收缩的直接影响。在此,我们旨在研究白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)对子宫收缩的直接影响,以确定它们是否像报道的脂多糖(LPS)和其他影响一样具有可立即观察到的作用。 研究方法 采用张力记录评估细胞因子和/或 LPS 对小鼠子宫收缩的直接影响。采用钙成像技术观察细胞因子处理过的子宫平滑肌细胞(MSMC)在催产素作用下的钙振荡。使用 Luminex 研究了应用 LPS 和/或细胞因子后子宫外胚层炎症细胞因子和趋化因子的释放情况。 结果 IL-1β、IL-6 和 TNF-α 能迅速增强足月妊娠小鼠子宫的收缩。与单独使用 LPS 相比,LPS 与 TNF-α 联合使用可增强子宫收缩,但这一效果在统计学上并不显著(p > 0.050)。用 IL-1β、IL-6 或 TNF-α 预处理 MSMC,可增加催产素作用下的钙振荡。LPS 和/或细胞因子可显著刺激子宫外植体释放 IL-1β、IL-6、TNF-α、趋化因子(C-X-C 矩阵)配体 1(CXCL1)和单核细胞趋化蛋白-1(MCP1)。 结论 炎性细胞因子对小鼠子宫收缩有短期和长期的影响,它们共同促成了分娩过程中逐渐增强的子宫收缩。
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引用次数: 0
期刊
American Journal of Reproductive Immunology
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