Cervicovaginal immune factors throughout the menstrual cycle: analysis of a cohort of Kenyan adolescents, systematic review, and meta-analysis

整个月经周期的宫颈阴道免疫因素：肯尼亚青少年队列分析、系统评价和荟萃分析

• 批准号: 10222496
• 负责人: Florian Hladik
• 金额: $ 8.83万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-23 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10222496
• 关键词: Address; Adolescent; Affect; Age; Antigens; Bacterial Vaginosis; Biological; Biological Assay; Biological Response Modifiers; Biology; Chlamydia; Complement; Conflict (Psychology); Data; Disease susceptibility; Environment; Equilibrium; Ethnic Origin; Foundations; Future; Goals; Gonorrhea; HIV; Health; Hormonal; Hormones; Human; Immune; Immunity; Immunologic Factors; Immunologics; Immunology; Inner Cell Mass; Intervention; Intervention Studies; Irrigation; Knowledge; Laboratories; Logistics; Luteal Phase; Measures; Menstrual cycle; Menstruation; Meta-Analysis; Methodology; Methods; Mucous Membrane; Outcome; Participant; Phase; Predisposition; Prevention strategy; Progesterone; Prophylactic treatment; Proteins; Publishing; Race; Reporting; Research; Research Personnel; Resources; STI prevention; Sampling; Schedule; Seminal fluid; Serum; Sexually Transmitted Diseases; Shapes; Site; Specimen; Swab; Techniques; Testing; Validation; Variant; Woman; base; cervicovaginal; cohort; genital herpes; hormonal contraception; inclusion criteria; infection risk; meetings; microbiota; mucosal vaccination; pathogen; primary outcome; proliferative phase Menstrual cycle; reproductive tract; secondary outcome; sperm cell; systematic review

PROJECT SUMMARY/ABSTRACT Quantifying immune mediators within the cervicovaginal tract (CVT) enables researchers to assess women's susceptibility to HIV and other sexually transmitted infections (STIs). Nearly twenty studies have been published describing how immune factors in the CVT change during the menstrual cycle. Despite this abundance of data, we lack a clear picture of the immune changes that occur, and it remains completely unknown whether a specific phase in the menstrual cycle is associated with increased disease susceptibility. This knowledge gap has important implications for research on interventions to reduce STI risk in women. The primary goal of this project is to gain a comprehensive understanding of how menstrual cycle phase affects immune factor concentrations in the CVT. Our first aim is to perform a systematic review and meta-analysis of studies that have quantified immune mediators from CVT specimens during the luteal and follicular phases of the menstrual cycle in women who are not using hormonal contraception. Our preliminary data indicate that there are at least seventeen published studies meeting inclusion criteria. In addition to assessing variation during the menstrual cycle, we will also assess the impact of bacterial vaginosis, STIs (genital herpes, gonorrhea, and chlamydia), race/ethnicity, and age. We will address technical questions of key importance to the field, including the effect of CVT sample type, assay type, method of determining menstrual phase, and data normalization technique. Our second aim is to extend and validate the meta-analysis using samples from a cohort of 119 Kenyan adolescents ages 16-20 years (with a total of 200 samples). We will use preliminary results from our first aim to inform which immune factors we select for the Kenyan cohort, to both increase the number of immune factors that can be included in the meta-analysis and validate the most important findings. We then plan to add results of this aim to the meta-analysis. As we show in our preliminary data, by combining data from many studies, we can gain a comprehensive understanding of mucosal immune changes that impact women's susceptibility to STIs. Understanding these changes will provide an important foundation for future studies of health interventions (such as STI prevention strategies, HIV prophylaxis, or hormonal contraception) and drive future research in the basic immunology of the CVT.

项目摘要/摘要 量化宫颈阴道区内的免疫介质（CVT）使研究人员能够评估 妇女对艾滋病毒和其他性传播感染的敏感性（STIS）。近二十个研究 已经发表了描述月经周期中CVT中的免疫因子如何变化的发表。 尽管有很多数据，但我们对发生的免疫变化缺乏清晰的了解，并且 仍然未知月经周期中的特定阶段是否与 疾病易感性提高。这种知识差距对研究的重要意义 降低女性性传播感染风险的干预措施。该项目的主要目标是获得全面的 了解月经循环阶段如何影响CVT中的免疫因子浓度。我们的第一个 目的是对已量化免疫的研究进行系统的综述和荟萃分析 女性月经周期的黄体和卵泡相期间CVT标本的介体 不使用荷尔蒙避孕的人。我们的初步数据表明至少有 十七个发表的研究符合纳入标准。除了评估差异 月经周期，我们还将评估细菌性阴道病，性传播疾病的影响（生殖器疱疹，淋病， 和衣原体），种族/种族和年龄。我们将解决有关关键的技术问题 字段，包括CVT样本类型的效果，测定类型，确定月经相的方法和 数据归一化技术。我们的第二个目的是使用 来自119名肯尼亚青少年16-20岁的肯尼亚青少年队列的样本（共有200个样本）。我们 将使用我们第一个目标的初步结果来告知我们为肯尼亚选择哪些免疫因素 队列，以增加可以包括在荟萃分析和 验证最重要的发现。然后，我们计划将该目标的结果添加到荟萃分析中。像我们 在我们的初步数据中显示，通过结合许多研究的数据，我们可以获得全面的 了解粘膜免疫变化，影响妇女对性传播感染的敏感性。理解 这些变化将为未来的健康干预措施提供重要基础（例如 STI预防策略，预防HIV或激素避孕）并推动未来的研究 CVT的基本免疫学。