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

项目总结/摘要 量化宫颈阴道道（CVT）内的免疫介质使研究人员能够评估 妇女易感染艾滋病毒和其他性传播感染。近20项研究 已经发表了描述CVT中的免疫因子在月经周期期间如何变化的文章。 尽管有如此丰富的数据，我们仍然缺乏对免疫变化的清晰描述， 仍然完全不清楚月经周期中的特定阶段是否与 增加疾病易感性。这一知识差距对以下方面的研究具有重要意义： 采取干预措施，降低妇女的性传播感染风险。该项目的主要目标是获得全面的 了解月经周期阶段如何影响CVT中的免疫因子浓度。我们的第一 目的是对量化免疫功能的研究进行系统回顾和荟萃分析， 女性月经周期黄体期和卵泡期CVT标本中的介质 不使用激素避孕的人我们的初步数据显示， 17项已发表的研究符合纳入标准。除了评估期间的变化外， 月经周期，我们还将评估细菌性阴道病，性传播感染（生殖器疱疹，淋病， 和衣原体）、种族/民族和年龄。我们将讨论对本组织至关重要的技术问题， 包括CVT样品类型、测定类型、确定月经期的方法的影响，以及 数据规范化技术我们的第二个目标是扩展和验证荟萃分析， 样本来自119名16-20岁的肯尼亚青少年（共200个样本）。我们 我将使用我们第一个目标的初步结果来告知我们为肯尼亚人选择哪些免疫因子。 队列，以增加可纳入荟萃分析的免疫因子数量， 验证最重要的发现。然后，我们计划将这一目标的结果添加到荟萃分析中。正如我们 我们的初步数据显示，通过结合多项研究的数据，我们可以获得一个全面的 了解影响妇女对性传播感染易感性的粘膜免疫变化。理解 这些变化将为未来的健康干预研究提供重要的基础（如 性传播感染预防战略、艾滋病毒预防或激素避孕），并推动未来在 CVT的基本免疫学

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.