Effect of B-cell depletion on vaginal microbiota and mucosal immunity
B 细胞耗竭对阴道微生物群和粘膜免疫的影响
基本信息
- 批准号:10374759
- 负责人:
- 金额:$ 25.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-19 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:AgeAnimalsAntibodiesAreaAtopobium vaginaeAutoantibodiesAutoimmune DiseasesB-LymphocytesBacteriaBindingBiologicalBiologyCaringCell CountCellsCervicalClinicalCommunitiesDataDiagnosisDropsEnrollmentEnvironmentEpithelial CellsEpitopesEscherichia coliEtiologyExperimental ModelsFemale genitaliaGardnerella vaginalisGrantHomeostasisHumanImmuneImmunityImmunoglobulin AImmunoglobulin GImmunoglobulin-Secreting CellsImmunoglobulinsImmunologic MarkersInfection ControlInflammationInflammatoryIntravenous ImmunoglobulinsKnowledgeLactobacillusLeadLow Birth Weight InfantMS4A1 geneMeasurementMeasuresMonoclonal AntibodiesMorbidity - disease rateMucosal Immune ResponsesMucosal ImmunityMucositisMucous MembraneMusObservational StudyOutcomePainPlasma CellsPlayPopulationPregnancyPremature BirthRegulationReproductive HealthRiskRoleSamplingSecretory Immunoglobulin ASexually Transmitted DiseasesSpontaneous abortionStreptococcusStreptococcus Group BSurfaceSymptomsTestingTimeVaginaVaginal DischargeVaginitisWomananti-CD20chemokinecohortcytokinedensitydesigndysbiosisexperienceexperimental studygut microbiotahigh riskhost-microbe interactionsimmunoregulationimplantationin vivoineffective therapiesinflammatory markermicrobial communitymicrobiomemicrobiotanovelnovel strategiespathobiontreproductive outcomereproductive tractrestorationrituximabtositumomabvaginal fluidvaginal lactobacillivaginal microbiomevaginal microbiotavaginal mucosa
项目摘要
PROJECT SUMMARY
The vaginal microbiome plays a significant role in reproductive health outcomes, influencing a woman’s chances
of pregnancy implantation, miscarriage, low birth weight, preterm delivery, and acquisition of sexually transmitted
infections. While many studies have shown that changes in the female genital tract (FGT) microbiota drive
changes in the mucosal immune environment, there are few studies that have explored the alternate possibility:
that changes in host mucosal immunity determine the composition of the vaginal microbial community. We have
described a Lactobacillus-deficient, inflammatory vaginitis in women treated with rituximab, an anti-CD20
antibody which leads to systemic B-cell depletion. This observation led us to hypothesize that B-cells and
vaginal fluid antibodies regulate the composition of the vaginal microbiota, controlling levels of
pathobionts such as E. coli and Group B streptococcus and facilitating Lactobacillus dominance.
Although associations between B-cells, antibodies and microbiota have been described in the gut, this is an
unexplored area in the female genital tract. Our proposed project is novel in both exploring the role of B-cells
and antibodies in regulation of vaginal microbiota, but also in using clinical rituximab treatment as an in vivo
experimental model. This exploratory grant has potential to identify highly significant biologic mechanisms for
regulation of FGT microbiota and mucosal inflammation, both of which are associated with adverse reproductive
health outcomes. To test our hypothesis, we propose an observational study comparing women treated with
rituximab to healthy controls to identify the role of B-cells in determining the composition of the vaginal microbiota.
In Aim 1 we will compare the vaginal microbiota, cervical immune cells, vaginal fluid immunoglobulins and
soluble markers of inflammation between 40 women being treated with rituximab to 40 healthy controls. We will
also compare these markers between women being treated with rituximab with inflammatory vaginitis and those
without. In Aim 2, we will assess the causal relationship with B-cell depletion by comparing changes in our
measured analytes over time in women who are 1) starting, 2) stopping and 3) stable on treatment with rituximab
(n = 10 in each group). Our local vaginal measurements of immune cell populations and soluble markers will be
compared with systemic measurements of B-cell numbers and IgG levels. Using rituximab treatment as an in
vivo experimental model will provide a novel opportunity to examine the role of systemic immunity in regulating
the vaginal microbiota and mucosal immune responses, which will lead to broader understanding of both vaginal
and systemic mucosal immunity.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Caroline M Mitchell其他文献
Effect of the vaginal live biotherapeutic LACTIN-V (emLactobacillus crispatus/em CTV-05) on vaginal microbiota and genital tract inflammation among women at high risk of HIV acquisition in South Africa: a phase 2, randomised, placebo-controlled trial
阴道活菌治疗剂 LACTIN-V(嗜酸乳杆菌crispatus/CTV-05)对南非 HIV 感染高风险女性阴道微生物群和生殖道炎症的影响:一项 2 期、随机、安慰剂对照试验
- DOI:
10.1016/j.lanmic.2024.101037 - 发表时间:
2025-06-01 - 期刊:
- 影响因子:20.400
- 作者:
Anke Hemmerling;Caroline M Mitchell;Suuba Demby;Musie Ghebremichael;Joseph Elsherbini;Jiawu Xu;Nondumiso Xulu;Johnathan Shih;Krista Dong;Vaneshree Govender;Vanessa Pillay;Nasreen Ismail;Gardenia Casillas;Jayajothi Moodley;Agnes Bergerat;Tess Brunner;Lenine Liebenberg;Sinaye Ngcapu;Ian Mbano;Laurel Lagenaur;Craig R Cohen - 通讯作者:
Craig R Cohen
Caroline M Mitchell的其他文献
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{{ truncateString('Caroline M Mitchell', 18)}}的其他基金
Vaginal microbiota transplant to promote Lactobacillus-dominant cervicovaginal communities
阴道微生物群移植促进以乳杆菌为主的宫颈阴道群落
- 批准号:
10366355 - 财政年份:2021
- 资助金额:
$ 25.2万 - 项目类别:
Novel mechanisms of pathogenesis in idiopathic vaginitis
特发性阴道炎发病机制的新机制
- 批准号:
9107790 - 财政年份:2015
- 资助金额:
$ 25.2万 - 项目类别:
Novel mechanisms of pathogenesis in idiopathic vaginitis
特发性阴道炎发病机制的新机制
- 批准号:
8969791 - 财政年份:2015
- 资助金额:
$ 25.2万 - 项目类别:
Female Genital Innate Immune Response to Vaginal Microbiota
女性生殖器对阴道微生物群的先天免疫反应
- 批准号:
8447048 - 财政年份:2010
- 资助金额:
$ 25.2万 - 项目类别:
Female Genital Innate Immune Response to Vaginal Microbiota
女性生殖器对阴道微生物群的先天免疫反应
- 批准号:
8636983 - 财政年份:2010
- 资助金额:
$ 25.2万 - 项目类别:
Female Genital Innate Immune Response to Vaginal Microbiota
女性生殖器对阴道微生物群的先天免疫反应
- 批准号:
8049622 - 财政年份:2010
- 资助金额:
$ 25.2万 - 项目类别:
Female Genital Innate Immune Response to Vaginal Microbiota
女性生殖器对阴道微生物群的先天免疫反应
- 批准号:
7869806 - 财政年份:2010
- 资助金额:
$ 25.2万 - 项目类别:
Female Genital Innate Immune Response to Vaginal Microbiota
女性生殖器对阴道微生物群的先天免疫反应
- 批准号:
8239587 - 财政年份:2010
- 资助金额:
$ 25.2万 - 项目类别:
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