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The Effect of Oral Cyclosporine A on Immune Indicators and Pregnancy Outcomes in Patients With Adverse Pregnancies: A Retrospective Study 口服环孢素A对不良妊娠患者免疫指标和妊娠结局影响的回顾性研究
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-19 DOI: 10.1111/aji.70210
Maojiao Wang, Zhongchao Fu, Rangeng Shi, Peng Zhang, Shiqi Lin, Jiang Liu, Chenli Ye, Weiling Cao, Xiaogui Cheng

Aim

The use of low-dose cyclosporine A (CsA) has been shown to increase live birth rates in cases of unexplained recurrent spontaneous abortions, without causing significant side effects for the pregnant woman or fetus. The primary aim of this study was to evaluate the effect of CsA on immune system indicators and pregnancy success in adverse pregnancies.

Methods

Data were collected from patients diagnosed with adverse pregnancies caused by immune-related abnormalities at the Department of Rheumatology and Immunology in a tertiary hospital in Shenzhen, China, between September 2023 and October 2024. Information collected included patient details, cytokine levels, lymphocyte subpopulations, blocking antibody changes, and CsA blood concentration during medication. This helped determine the effective blood concentration range of CsA for these patients, aimed at enhancing the drug's safety and effectiveness.

Outcome

The study included a total of 661 participants, among whom 279 achieved successful pregnancies after CsA treatment (A clinically confirmed pregnancy is considered a successful pregnancy). The CD3+, CD4+, and CD8+ blocking antibody efficiency levels were significantly increased after CsA administration (P < 0.001, p = 0.003, p = 0.017), and the former two changes were strongly correlated with pregnancy success (p = 0.002, P < 0.001). The receiver operating characteristic (ROC) curve revealed that increases in CD3+, CD4+ blocking antibodies were strong predictors of successful pregnancy outcomes. Cytokine levels, including IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α, decreased significantly after treatment (P < 0.01). Ratios such as IL-2/IL-10 and IFN-γ/IL-10 also showed significant reductions (P < 0.001), while the IFN-γ/IL-4 and TNF-α/IL-4 ratios increased significantly (P < 0.001). The majority of patients had blood CsA concentrations between 10–70 ng/mL.

Conclusion

These findings suggest that CsA can effectively regulate immune markers and restore immune balance, reducing the impact of immune-related adverse pregnancy outcomes.

目的:使用低剂量环孢素A (CsA)已被证明可增加原因不明的复发性自然流产病例的活产率,而不会对孕妇或胎儿造成明显的副作用。本研究的主要目的是评估CsA对不良妊娠免疫系统指标和妊娠成功率的影响。方法:收集2023年9月至2024年10月在中国深圳某三级医院风湿病免疫科诊断为免疫相关异常导致的不良妊娠患者的数据。收集的信息包括患者详细信息、细胞因子水平、淋巴细胞亚群、阻断抗体变化和用药期间CsA血药浓度。这有助于确定这些患者CsA的有效血药浓度范围,旨在提高药物的安全性和有效性。结果:本研究共纳入661例受试者,其中279例经CsA治疗后妊娠成功(临床证实妊娠为成功妊娠)。CsA给药后CD3+、CD4+、CD8+阻断抗体水平均显著升高(P < 0.001, P = 0.003, P = 0.017),且CD3+、CD4+和CD8+阻断抗体水平与妊娠成功率密切相关(P = 0.002, P < 0.001)。受试者工作特征(ROC)曲线显示,CD3+、CD4+阻断抗体的升高是成功妊娠结局的有力预测因子。治疗后细胞因子IL-2、IL-4、IL-6、IL-10、IL-17、IFN-γ、TNF-α水平均显著降低(P < 0.01)。IL-2/IL-10和IFN-γ/IL-10比值也显著降低(P < 0.001), IFN-γ/IL-4和TNF-α/IL-4比值显著升高(P < 0.001)。大多数患者血CsA浓度在10-70 ng/mL之间。结论:CsA可有效调节免疫标志物,恢复免疫平衡,降低免疫相关不良妊娠结局的影响。
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引用次数: 0
Comment on: “Study on the Effects of Doxycycline Treatment on Endometrial Microbiota and Pregnancy Outcomes in Chronic Endometritis”: Beyond Composition: The Potential Role of Microbial Load in CE Pathophysiology 评论:“多西环素治疗对慢性子宫内膜炎子宫内膜微生物群和妊娠结局影响的研究”:超越成分:微生物负荷在CE病理生理中的潜在作用。
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-13 DOI: 10.1111/aji.70204
Yinglan Ma, Qun Zhou, Huilin Yang
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引用次数: 0
Nicotinamide Riboside Mitigates Antiphospholipid Antibody-Induced Dysfunction in Human Trophoblast Cells 烟酰胺核苷减轻抗磷脂抗体诱导的人滋养细胞功能障碍。
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-12 DOI: 10.1111/aji.70205
Abigail C. Fischer, Hanah M. Georges, Deidre M. Jones, Lawrence W. Chamley, Vikki M. Abrahams

Problem

Obstetric antiphospholipid syndrome (APS) is characterized by the presence of circulating anti-phospholipid antibodies (aPL), which disrupt early placentation and contribute to adverse pregnancy outcomes including pregnancy loss and preterm birth. aPL, specifically those targeting beta 2 glycoprotein 1 (β2GPI), interact with placental trophoblast cells and induce inflammation, disrupt angiogenic factor production, and reduce cell migration. In addition, aPL have been shown to promote a state of oxidative stress in trophoblast cells and in APS patients. This study aimed to investigate if the antioxidant, nicotinamide riboside (NR), could mitigate the negative effects of aPL on trophoblast cells.

Method of Study

The human first-trimester trophoblast cell line, Sw.71, was treated with or without aPL in the presence or absence of NR. Trophoblast supernatants were measured by ELISA for pro-inflammatory cytokines/chemokines and angiogenic factors. Cell migration was measured using a two-chamber colorimetric assay. ROS production was measured using a fluorescence assay.

Results

NR blocked aPL-induced trophoblast inflammation and ROS production, and reversed the effects of aPL on trophoblast angiogenic factor production. However, NR was unable to rescue aPL-induced trophoblast migratory dysfunction.

Conclusion

NR mitigated some, but not all, aPL-induced trophoblast dysfunction. This provides new insight into the role of antioxidant therapies on aPL-induced pregnancy complications, and a possible new avenue of managing obstetric APS to explore further.

问题:产科抗磷脂综合征(APS)的特点是存在循环抗磷脂抗体(aPL),它会破坏早期胎盘,并导致包括妊娠丢失和早产在内的不良妊娠结局。aPL,特别是靶向β2糖蛋白1 (β2GPI)的aPL,与胎盘滋养细胞相互作用,诱导炎症,破坏血管生成因子的产生,并减少细胞迁移。此外,aPL已被证明可促进滋养细胞和APS患者的氧化应激状态。本研究旨在探讨抗氧化剂烟酰胺核苷(nicotinamide riboside, NR)是否能减轻aPL对滋养细胞的负面影响。研究方法:将人妊娠早期滋养细胞sw71在有或没有NR的情况下用aPL处理或不加aPL。用ELISA法检测滋养细胞上清中促炎细胞因子/趋化因子和血管生成因子。采用双室比色法测定细胞迁移。用荧光法测定ROS的产生。结果:NR阻断aPL诱导的滋养细胞炎症和ROS生成,逆转aPL对滋养细胞血管生成因子生成的影响。然而,NR无法挽救apl诱导的滋养细胞迁移功能障碍。结论:NR减轻了部分(但不是全部)apl诱导的滋养细胞功能障碍。这为抗氧化治疗在apl诱导的妊娠并发症中的作用提供了新的见解,并为进一步探索产科APS的管理提供了可能的新途径。
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引用次数: 0
Impact of Anti-Endometrial Antibodies on IVF Implantation and Pregnancy Outcomes: A Retrospective Study 抗子宫内膜抗体对体外受精着床和妊娠结局影响的回顾性研究。
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-08 DOI: 10.1111/aji.70202
Xiaoxuan Yang, Yan Su, Yaping Guo, Mianqiu Zhang, Juan Zhang, Xiaojing Hou, Shuangshuang Zhao, Huiqing An, Xiufeng Ling, Rong Shen

Problems

To investigate the impact of anti-endometrial antibodies (EMAb) on pregnancy outcomes in infertile patients undergoing in vitro fertilization (IVF) and to assess the potential value of personalized treatment strategies.

Method of Study

A total of 47 EMAb-positive and 166 EMAb-negative oocyte retrieval cycles were retrospectively included following propensity score matching (PSM) to control for basic clinical characteristics influencing pregnancy outcomes. The two groups were compared in terms of various aspects closely associated with IVF outcomes. Pregnancy outcomes were assessed based on implantation, clinical pregnancy, miscarriage, and ongoing pregnancy rates.

Results

No significant differences were found between the two groups regarding infertility-related clinical characteristics, oocyte- and embryo-related indicators, endometriosis incidence, and so forth. Compared with the EMAb-negative group, the implantation rate in the EMAb-positive group was lower by 10.3 percentage points (p = 0.047), whereas the 8.2-point lower clinical pregnancy rate did not reach statistical significance (p = 0.234). There were no significant differences in ongoing pregnancy and miscarriage rates between the two groups.

Conclusions

Our study observed that the presence of EMAb was associated with less favorable IVF outcomes, primarily reflected in lower implantation and clinical pregnancy rates. However, once the implantation was successful, the risk of miscarriage did not increase. These findings suggest a potential role for EMAb screening in guiding personalized treatment strategies, such as increasing the number of embryos transferred or using immunosuppressive agents, to improve IVF outcomes. Future research should involve more extensive and diverse populations to explore the mechanisms of action of EMAb and their impact on IVF treatment outcomes.

目的:探讨抗子宫内膜抗体(EMAb)对体外受精(IVF)不孕症患者妊娠结局的影响,并评估个性化治疗策略的潜在价值。研究方法:回顾性纳入47例emab阳性和166例emab阴性的卵母细胞回收周期,采用倾向评分匹配(PSM)来控制影响妊娠结局的基本临床特征。两组在与IVF结果密切相关的各个方面进行比较。根据植入、临床妊娠、流产和持续妊娠率评估妊娠结局。结果:两组在不孕相关临床特征、卵母细胞及胚胎相关指标、子宫内膜异位症发生率等方面均无显著差异。与emab阴性组相比,emab阳性组着床率降低10.3个百分点(p = 0.047),而临床妊娠率降低8.2个百分点,差异无统计学意义(p = 0.234)。两组之间的持续妊娠率和流产率没有显著差异。结论:我们的研究发现,EMAb的存在与较差的IVF结果相关,主要体现在较低的着床率和临床妊娠率。然而,一旦植入成功,流产的风险并没有增加。这些发现表明,EMAb筛查在指导个性化治疗策略方面具有潜在作用,例如增加胚胎移植数量或使用免疫抑制剂,以改善体外受精结果。未来的研究应涉及更广泛和多样化的人群,以探索EMAb的作用机制及其对体外受精治疗结果的影响。
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引用次数: 0
Indications for Performing the APCA Test in Female Infertility 在女性不孕症中进行APCA试验的适应症。
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-07 DOI: 10.1111/aji.70206
Mojtaba Aghaei, Mehdi Torabizadeh, Mohammad Amin Vahid, Najmaldin Saki
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引用次数: 0
Identification and Subtype Analysis of Lipid Metabolism-Related Diagnostic Biomarkers for Endometriosis Based on WGCNA and Machine Learning 基于WGCNA和机器学习的子宫内膜异位症脂质代谢相关诊断生物标志物的鉴定和亚型分析
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-23 DOI: 10.1111/aji.70201
Yingyi Guo, Yue Hou, Jinshuang Wu, Ning Lou, Dongxia Yang

Background

Endometriosis (EM), a disorder driven by persistent systemic inflammation, impacts around 10% of women in their reproductive period, often diagnosed only via surgery. Metabolic alterations, particularly in lipid metabolism, may uncover novel biomarkers. We aimed to identify diagnostic markers and molecular subtypes by integrating lipid metabolism gene expression and machine learning.

Methods

We downloaded gene expression datasets (GSE51981 and GSE7305) from the Gene Expression Omnibus (GEO) database. Differential expression was analyzed using limma (|log2FC| > 1, p.adj < 0.05); intersected with lipid genes to yield candidate genes. Weighted gene co-expression network analysis (WGCNA) demonstrated endometriosis-connected gene modules. Integrating lipid metabolism-related differentially expressed genes with WGCNA hub genes, followed by least absolute shrinkage and selection operator (LASSO) and XGBoost machine learning, identified diagnostic biomarkers. Their performance was validated using receiver operating characteristic (ROC) curves in an independent dataset. Immune infiltration, including CIBERSORT and single-sample GSEA (ssGSEA), gene set enrichment analysis (GSEA), and non-negative matrix factorization (NMF)-based subtype analyses were performed. MicroRNA (miRNA) and transcription factor (TF) regulatory networks were constructed using online databases.

Results

We identified 106 lipid metabolism-related differential genes. WGCNA revealed the turquoise module strongly correlated with endometriosis. ELOVL6 and MED20 were identified as key genes through machine learning algorithms. The two key genes emerged as robust diagnostic biomarkers, showing high area under the ROC curves (AUCs) across both training and validation sets. Immune infiltration analysis revealed distinct immune cell patterns in endometriosis, with ELOVL6 and MED20 correlating with specific immune cells. Subtype analysis, based on lipid metabolism scores, stratified patients into high and low score groups with differential gene expression and immune cell infiltration. Regulatory networks identified miRNAs and TFs targeting ELOVL6 and MED20.

Conclusion

Our study identified ELOVL6 and MED20 as promising lipid metabolism-related diagnostic biomarkers for endometriosis. We also uncovered distinct molecular subtypes linked to lipid metabolism, providing novel insights into endometriosis heterogeneity and potential therapeutic targets.

背景:子宫内膜异位症(EM)是一种由持续性全身性炎症引起的疾病,影响约10%的育龄妇女,通常只能通过手术诊断。代谢变化,特别是脂质代谢,可能会发现新的生物标志物。我们的目标是通过整合脂质代谢基因表达和机器学习来识别诊断标记和分子亚型。方法:从gene expression Omnibus (GEO)数据库下载基因表达数据集GSE51981和GSE7305。采用limma (|, log2FC, |, |, 1, p. 4)分析差异表达。结果:鉴定出106个脂质代谢相关差异基因。WGCNA显示绿松石模块与子宫内膜异位症密切相关。通过机器学习算法确定ELOVL6和MED20为关键基因。这两个关键基因成为了可靠的诊断性生物标志物,在训练集和验证集的ROC曲线下都显示出高面积。免疫浸润分析揭示了子宫内膜异位症不同的免疫细胞模式,ELOVL6和MED20与特异性免疫细胞相关。亚型分析以脂质代谢评分为基础,根据基因表达差异和免疫细胞浸润情况将患者分为高分组和低分组。调控网络确定了靶向ELOVL6和MED20的mirna和tf。结论:我们的研究确定ELOVL6和MED20是子宫内膜异位症有前途的脂质代谢相关诊断生物标志物。我们还发现了与脂质代谢相关的不同分子亚型,为子宫内膜异位症的异质性和潜在的治疗靶点提供了新的见解。
{"title":"Identification and Subtype Analysis of Lipid Metabolism-Related Diagnostic Biomarkers for Endometriosis Based on WGCNA and Machine Learning","authors":"Yingyi Guo,&nbsp;Yue Hou,&nbsp;Jinshuang Wu,&nbsp;Ning Lou,&nbsp;Dongxia Yang","doi":"10.1111/aji.70201","DOIUrl":"10.1111/aji.70201","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Endometriosis (EM), a disorder driven by persistent systemic inflammation, impacts around 10% of women in their reproductive period, often diagnosed only via surgery. Metabolic alterations, particularly in lipid metabolism, may uncover novel biomarkers. We aimed to identify diagnostic markers and molecular subtypes by integrating lipid metabolism gene expression and machine learning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We downloaded gene expression datasets (GSE51981 and GSE7305) from the Gene Expression Omnibus (GEO) database. Differential expression was analyzed using limma (|log<sub>2</sub>FC| &gt; 1, <i>p</i>.adj &lt; 0.05); intersected with lipid genes to yield candidate genes. Weighted gene co-expression network analysis (WGCNA) demonstrated endometriosis-connected gene modules. Integrating lipid metabolism-related differentially expressed genes with WGCNA hub genes, followed by least absolute shrinkage and selection operator (LASSO) and XGBoost machine learning, identified diagnostic biomarkers. Their performance was validated using receiver operating characteristic (ROC) curves in an independent dataset. Immune infiltration, including CIBERSORT and single-sample GSEA (ssGSEA), gene set enrichment analysis (GSEA), and non-negative matrix factorization (NMF)-based subtype analyses were performed. MicroRNA (miRNA) and transcription factor (TF) regulatory networks were constructed using online databases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 106 lipid metabolism-related differential genes. WGCNA revealed the turquoise module strongly correlated with endometriosis. ELOVL6 and MED20 were identified as key genes through machine learning algorithms. The two key genes emerged as robust diagnostic biomarkers, showing high area under the ROC curves (AUCs) across both training and validation sets. Immune infiltration analysis revealed distinct immune cell patterns in endometriosis, with ELOVL6 and MED20 correlating with specific immune cells. Subtype analysis, based on lipid metabolism scores, stratified patients into high and low score groups with differential gene expression and immune cell infiltration. Regulatory networks identified miRNAs and TFs targeting ELOVL6 and MED20.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study identified ELOVL6 and MED20 as promising lipid metabolism-related diagnostic biomarkers for endometriosis. We also uncovered distinct molecular subtypes linked to lipid metabolism, providing novel insights into endometriosis heterogeneity and potential therapeutic targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809213","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}
引用次数: 0
Immunological and Coagulation Predictors of Subchorionic Hematoma in Recurrent Pregnancy Loss: A Predictive Modeling Approach 复发性妊娠丢失中绒毛膜下血肿的免疫学和凝血预测:一种预测模型方法。
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-20 DOI: 10.1111/aji.70200
Xue Wei, Cai Liu, Weijing Wang, Lu Jiang, Fang Wang

Problem

Subchorionic hematoma (SCH) is a common complication in early pregnancy, particularly in women with recurrent pregnancy loss (RPL), and is associated with adverse pregnancy outcomes. However, reliable predictive tools for SCH in this high-risk group are lacking. The aim of this study was to identify coagulation and immune-related predictors associated with SCH in women with RPL and to construct a predictive model.

Method of Study

A retrospective analysis was performed on 1002 patients with RPL in the Reproductive Medicine Center of the Second Hospital of Lanzhou University. Clinical data, coagulation indicators, thromboelastography (TEG), and immunity indicators were collected. Predictors were selected via LASSO and logistic regression, and a LightGBM model was developed and validated.

Results

Eleven predictors were included in the final model: age, BMI, previous pregnancy losses, TEG-lysis index at 30 min, TEG- maximum amplitude, serum immunoglobulins IgG, complement C3, antiβ2 glycoprotein 1 antibody, rheumatoid factor IgM and interleukin-2/interleukin-6, interferon-γ/interleukin-6. The model demonstrated moderate and stable discrimination with AUCs of 0.745, 0.653, and 0.647 in the training, internal, and external validation sets, respectively.

Conclusions

The model effectively identifies SCH risk in RPL patients and informs individualized monitoring and early intervention strategies in clinical practice.

问题:绒毛膜下血肿(SCH)是妊娠早期常见的并发症,特别是在复发性妊娠丢失(RPL)的妇女中,并与不良妊娠结局相关。然而,在这一高危人群中,缺乏可靠的SCH预测工具。本研究的目的是确定与RPL女性SCH相关的凝血和免疫相关预测因素,并构建预测模型。研究方法:对兰州大学第二医院生殖医学中心1002例RPL患者进行回顾性分析。收集临床资料、凝血指标、血栓弹性成像(TEG)和免疫指标。通过LASSO和logistic回归选择预测因子,建立LightGBM模型并进行验证。结果:最终模型纳入了11个预测因素:年龄、BMI、既往妊娠损失、30 min时TEG-lysis指数、TEG- maximum amplitude、血清免疫球蛋白IgG、补体C3、抗β2糖蛋白1抗体、类风湿因子IgM和白细胞介素2/白细胞介素6、干扰素-γ/白细胞介素6。该模型在训练集、内部验证集和外部验证集上的auc分别为0.745、0.653和0.647,具有中等和稳定的判别能力。结论:该模型有效地识别了RPL患者的SCH风险,为临床实践提供了个性化监测和早期干预策略。
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引用次数: 0
Abandoning Reproductive Science Betrays Us All 放弃生殖科学背叛了我们所有人。
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-20 DOI: 10.1111/aji.70199
Jessica Weng, Jennifer L. Wayland, Indira U. Mysorekar, Elizabeth A. Bonney
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引用次数: 0
HIV-Exposed Seronegative Female Sex Workers Show Different Cellular Immune Profiles Across the Menstrual Cycle hiv暴露的血清阴性女性性工作者在月经周期中表现出不同的细胞免疫特征。
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-19 DOI: 10.1111/aji.70198
Monika M. Kowatsch, Kenneth Omollo, Frideborg Bradley, Anna Månberg, Peter Nilsson, Sofia Bergström, Julius Oyugi, Joshua Kimani, Kristina Broliden, Keith R. Fowke, Julie Lajoie

Problem

Female sex workers (FSWs) are at higher risk of acquiring HIV. Interestingly, some FSWs who are highly exposed remain seronegative for HIV (HESN). This natural resistance to HIV infection has been attributed to an immune quiescence (IQ) phenotype. Our study investigates how the menstrual cycle phases (follicular and luteal) impact the immune responses in Kenyan FSWs.

Methods

This is a part of the Longitudinal Assessment of Mucosal Immune Quiescence study (LAMIQ), 48 FSWs not living with HIV and not using hormonal contraception were followed for a menstrual cycle and divided into two groups based on duration of sex work: New Negative (NN) with 3 years or less and HESN with at least 7 years of involvement in sex work. We obtained blood and cervicovaginal samples and measured sex hormone, cytokine, and chemokine levels, and blood and endocervical T-cell and NK-cell phenotypes.

Results

We observed differences in how the immune response of NN and HESN responds to sex hormones. Indeed, the level of mucosal Annexin A3 measured was higher during the luteal phase in HESN, which was not observed in NN. HESN exhibited a higher CD39 expression on their Treg during the luteal phase, while maintaining CTLA-4 expression compared to NN. Furthermore, in HESN, NK cell activation varied across the menstrual cycle phases. They had a higher expression of NKG2D and an increase in the cluster of CD95+ HLA-DR+ NK cells during the follicular phase. This suggests stronger innate immune activation in HESN during the follicular phase of the menstrual cycle.

Conclusion

Our data indicate that, in HESN, there is a modulation of the immune response based on the menstrual cycle, which potentially limits the availability of HIV target cells at the female genital tract during the luteal phase of the menstrual cycle (window of susceptibility).

问题:女性性工作者(FSWs)感染艾滋病毒的风险更高。有趣的是,一些高度暴露于HIV的女工血清HIV (HESN)仍然呈阴性。这种对HIV感染的自然抵抗力归因于免疫静止(IQ)表型。我们的研究调查了月经周期阶段(卵泡和黄体)如何影响肯尼亚fsw的免疫反应。方法:这是粘膜免疫静止研究纵向评估(LAMIQ)的一部分,48名未感染艾滋病毒且未使用激素避孕的FSWs被跟踪一个月经周期,并根据性工作持续时间分为两组:新阴性(NN), 3年或以下,HESN,至少从事性工作7年。我们获得了血液和宫颈阴道样本,并测量了性激素、细胞因子和趋化因子水平,以及血液和宫颈内t细胞和nk细胞表型。结果:我们观察了神经网络和HESN对性激素的免疫反应的差异。事实上,在HESN的黄体期,粘膜膜联蛋白A3的水平更高,而在NN中没有观察到这一点。与NN相比,HESN在黄体期Treg上CD39表达较高,同时CTLA-4表达维持不变。此外,在HESN中,NK细胞激活在月经周期各阶段有所不同。在卵泡期,它们具有更高的NKG2D表达和CD95+ HLA-DR+ NK细胞簇的增加。这表明在月经周期的卵泡期,HESN的先天免疫激活更强。结论:我们的数据表明,在HESN中,存在基于月经周期的免疫应答调节,这可能限制了月经周期黄体期(易感窗口)女性生殖道中HIV靶细胞的可用性。
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引用次数: 0
Extracellular Vesicles for the Maintenance of Pregnancies in Situations of Recurrent Spontaneous Abortion: Scoping Review 细胞外囊泡在反复自然流产情况下维持妊娠的作用:范围综述。
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-12-17 DOI: 10.1111/aji.70197
Marcelo Garrido, Francisco Monico Moreira, Luis Antonio Gilberti Panucci, Graziela Garrido Mori

Purpose

Given the immune system's role in pregnancy, the immunomodulation generated by the use of extracellular vesicles (EVs) has been considered a possible treatment in situations of recurrent spontaneous abortion (RSA). Thus, this study evaluated, through a scoping review, the applicability of extracellular vesicle therapies for immunomodulation in maintaining pregnancies in situations of RSA.

Methods

This study was based on the Guidance for Conducting Systematic Scoping Reviews and was registered on the OSF Home platform. A systematic search was performed in the PubMed/MEDLINE, Scopus, and Cochrane Library databases up to June 2025 by two independent reviewers to answer the question addressed in the present review.

Results

A total of 440 articles were analyzed, and after applying the eligibility criteria and excluding duplicate studies, three studies were selected. All three studies showed reduced embryonic absorption, promoting pregnancy maintenance. The EVs were extracted from trophoblasts, decidual stromal cells, or bone marrow stem cells, and administered intravenously, primarily, in dose of 100 or 200 µg. All EVs have immunomodulatory relevance in pregnancy, modifying the lymphocyte and cytokine patterns, and contributing to angiogenesis and trophoblast growth.

Conclusion

We conclude that EVs represent a potential area for the development of future therapies for pregnancies with RSA, and new studies are necessary to confirm these findings.

鉴于免疫系统在妊娠中的作用,利用细胞外囊泡(EVs)产生的免疫调节被认为是治疗复发性自然流产(RSA)的一种可能的方法。因此,本研究通过范围综述,评估了细胞外囊泡治疗在RSA情况下维持妊娠的免疫调节的适用性。方法:本研究依据《进行系统范围审查指南》,并在OSF Home平台注册。系统检索PubMed/MEDLINE、Scopus和Cochrane图书馆数据库至2025年6月,由两名独立审稿人回答本综述中提出的问题。结果:共分析440篇文献,应用入选标准并排除重复研究后,筛选出3篇研究。所有三项研究都表明,减少胚胎吸收,促进妊娠维持。从滋养细胞、蜕质细胞或骨髓干细胞中提取ev,主要以100或200µg的剂量静脉注射。所有EVs在妊娠中都具有免疫调节作用,改变淋巴细胞和细胞因子的模式,促进血管生成和滋养细胞的生长。结论:我们得出结论,EVs代表了未来治疗妊娠RSA的潜在领域,需要新的研究来证实这些发现。
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引用次数: 0
期刊
American Journal of Reproductive Immunology
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