Systemic and mucosal immune dysregulation and HIV risk in transgender females

项目概要/摘要： 与男性发生性关系的跨性别女性（TFSM）和男性是一个不成比例地受到 艾滋病毒/艾滋病流行。虽然经常被归为顺男同性恋者（男男性行为者）， TFSM具有独特的免疫表型，这是由于TFSM终生暴露于女性 性激素如雌二醇（E2）。由于E2可以调节多种全身和粘膜免疫参数， 对于确定那些遗传上是男性的人长期接触合成雌激素是否会产生不利影响， 影响艾滋病毒易感性。 目前，关于长期合成E2治疗对全身性炎症的影响程度， 免疫应答和直肠粘膜免疫微环境，包括微生物组， 艾滋病毒感染。该建议的目的是确定系统和粘膜免疫途径的失调 与感染艾滋病毒的风险有关。我们将评估艾滋病毒未感染的TFSM谁开始性别- 确认激素治疗（GAHT），并在3个月后随访（队列1），以及那些 接受GAHT治疗至少1年（队列2）。这项研究设计使我们能够比较免疫条件和功能， TFSM无E2治疗、短期E2治疗和长期E2治疗。 我们通过惠特曼临床研究主任Goldstein博士， 步行者研究所，华盛顿特区，谁是积极参与跨性别健康研究和共同研究员 这个提议。我们建议每组招募30-40名参与者，并收集血液用于全身免疫分析。 免疫应答和直肠拭子用于分析粘膜免疫微环境和微生物组。 美国国立卫生研究院（NIH）对资助跨性别研究的兴趣越来越大。然而，在这方面， 我们对可能影响艾滋病毒感染的免疫生物学机制的理解严重缺乏数据， TFSM。此外，该提案是对最近发布的NOSI，NOT-MD-19-001（健康研究）的回应。 性和性别少数群体（SGM）。 从这项研究中获得的数据的评估将刺激进一步的研究，可能会提醒科学和医学 这是一个未被探索的风险社区，并导致充分知情的建议和干预措施。

Project Summary/Abstract: Trans-females who have sex with men (TFSM) and men are a population disproportionately affected by the HV/AIDS epidemic. Although often grouped together with cis-men who have sex with men (MSM) due to the practice of receptive anal intercourse, TFSM have a unique immune phenotype due to life-long exposure to female sex hormones such as estradiol (E2). As E2 can modulate multiple systemic and mucosal immune parameters, it is critical to determine whether long-term synthetic estrogen exposure in those who are genetically male, adversely impact HIV susceptibility. Currently, there is a gap in the knowledge as to the extent to which long-term synthetic E2 therapy affects systemic immune responsiveness, and rectal mucosal immune microenvironment including the microbiome, in the context of HIV infection. The goal of this proposal is to identify dysregulation in systemic and mucosal immune pathways that are relevant to the risks of acquiring HIV. We will evaluate HIV uninfected TFSM who are starting gender- affirming hormone therapy (GAHT) and follow them up after 3 months (cohort 1), as well as those who have been on GAHT for at least 1 year (cohort 2). This study design allows us to compare immune condition and function in TFSM without E2 therapy, with short-term E2 therapy and with long-term E2 therapy. We have unique access to this population through Dr. Goldstein, the Director of Clinical Research at Whitman Walker Institute, Washington DC, who is actively involved in transgender health research and a co-investigator on this proposal. We propose to recruit 30-40 participants per group and collect blood for analysis of systemic immune responses and rectal swabs for analysis of mucosal immune microenvironment and microbiome. There is a growing interest in the National Institutes of Health (NIH) toward funding transgender research. However, data is severely lacking in our understanding of immuno-biological mechanisms that may affect HIV acquisition in TFSM. Further, this proposal is responsive to the recently issued NOSI, NOT-MD-19-001 (Research on the Health of Sexual and Gender Minority (SGM) Populations). Assessment of data obtained from this study will spur further research that may alert the scientific and medical community of unexplored risks and lead to well-informed recommendations and interventions.