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

项目摘要/摘要 量化宫颈阴道部(CVT)内的免疫介质使研究人员能够评估 妇女对艾滋病毒和其他性传播感染(STI)的易感性。近二十项研究 已经发表了描述CVT中的免疫因素在月经周期中如何变化的文章。 尽管有如此丰富的数据，但我们缺乏发生免疫变化的清晰图景，而且它 仍然完全不清楚月经周期中的特定阶段是否与 疾病易感性增加。这一知识鸿沟对研究 降低女性性病风险的干预措施。这个项目的主要目标是获得一个全面的 了解月经周期如何影响CVT中的免疫因子浓度。我们的第一次 目的是对已量化免疫的研究进行系统回顾和荟萃分析 女性月经周期黄体和卵泡期CVT标本中的介体 不使用激素避孕药的人。我们的初步数据显示，至少有 符合纳入标准的17项已发表研究。除了评估期间的变化 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、 和衣原体感染)、种族/民族和年龄。我们将解决对 包括CVT样本类型、化验类型、月经时相判定方法的影响 数据标准化技术。我们的第二个目标是使用以下工具扩展和验证元分析 样本来自119名年龄在16-20岁的肯尼亚青少年(共200份样本)。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人选择了哪些免疫因子 队列，既增加了可纳入荟萃分析的免疫因素的数量，又增加了 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。因为我们 在我们的初步数据中显示，通过结合许多研究的数据，我们可以获得一个全面的 了解影响女性感染性病易感性的粘膜免疫变化。理解 这些变化将为今后对卫生干预措施的研究(如 性传播感染预防策略、艾滋病毒预防或荷尔蒙避孕)，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.