Systemic and mucosal immune dysregulation and HIV risk in transgender females

跨性别女性的全身和粘膜免疫失调和艾滋病毒风险

• 批准号: 9927104
• 负责人: Mimi Ghosh
• 金额: $ 20.06万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-20 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9927104
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Affect; Age; Anal Sex; Androgens; Animal Model; Behavioral; Biological; Biological Response Modifiers; Blood; Chronic; Clinical Research; Communities; Data; District of Columbia; Dose; Epidemic; Estradiol; Estrogens; Exposure to; Female; Funding; Gender; Goals; HIV; HIV Infections; HIV risk; Health; Immune; Immune response; Immune system; Impairment; In Vitro; Inflammation; Inflammation Mediators; Inflammatory; Institutes; Intervention; Knowledge; Lead; Life; Link; Long-Term Effects; Medical; Mental Depression; Mucous Membrane; Participant; Pathway interactions; Periodicity; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Population; Predisposition; Production; Recommendation; Reporting; Research; Research Design; Research Personnel; Risk; Risk Assessment; Sexual Health; Sexual and Gender Minorities; Stress; Swab; United States National Institutes of Health; Violence; Vulnerable Populations; Walkers; cis-female; cis-male; cohort; cytokine; design; dosage; dysbiosis; female sex hormone; follow-up; gender nonconforming; high risk; hormone therapy; hypothalamic-pituitary-adrenal axis; immune function; in vivo; interest; male; men; men who have sex with men; microbiome; negative affect; recruit; rectal; rectal microbiome; response; sex; social; social stigma; stressor; transgender; tumor-immune system interactions; xenoestrogen

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.

项目摘要/摘要： 与男性发生性关系的跨性别女性 (TFSM) 和男性是受性别影响尤为严重的人群 艾滋病毒/艾滋病流行。尽管经常与男男性行为者 (MSM) 归为一类，因为 接受性肛交实践中，TFSM 由于终生接触女性而具有独特的免疫表型 性激素，例如雌二醇（E2）。由于 E2 可以调节多种全身和粘膜免疫参数，因此 对于确定长期接触合成雌激素是否会对遗传男性产生不利影响至关重要 影响艾滋病毒易感性。 目前，对于长期合成 E2 治疗对全身系统的影响程度，人们的认识还存在差距。 免疫反应性和直肠粘膜免疫微环境（包括微生物组） 艾滋病毒感染。该提案的目标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相关。我们将评估未感染 HIV 的 TFSM，他们正在开始性别- 肯定激素疗法 (GAHT) 并在 3 个月后对其进行随访（队列 1），以及那些已经接受过肯定激素疗法的患者 接受 GAHT 至少 1 年（第 2 组）。这项研究设计使我们能够比较免疫状况和功能 没有 E2 治疗的 TFSM、短期 E2 治疗和长期 E2 治疗。 我们通过惠特曼临床研究总监戈德斯坦博士拥有独特的接触这一人群的机会 华盛顿特区沃克研究所，积极参与跨性别健康研究，也是 这个建议。我们建议每组招募30-40名参与者并采集血液用于系统免疫分析 反应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) 对资助跨性别研究越来越感兴趣。然而， 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 性和性别少数群体（SGM））。 对本研究获得的数据的评估将刺激进一步的研究，这可能会提醒科学和医学界 社区中未探索的风险，并产生明智的建议和干预措施。