Dataset Information

A Noninvasive Method to Sample Immune Cells in the Lower Female Genital Tract Using Menstrual Discs.

ABSTRACT: T cells in the human female genital tract (FGT) are key mediators of susceptibility to and protection from infection, including HIV and other sexually transmitted infections. There is a critical need for increased understanding of the distribution and activation of T cell populations in the FGT, but current sampling methods require a healthcare provider and are expensive, limiting the ability to study these populations longitudinally. To address these challenges, we have developed a method to sample immune cells from the FGT utilizing disposable menstrual discs which are noninvasive, self-applied, and low in cost. To demonstrate reproducibility, we sampled the cervicovaginal fluid of healthy, reproductive-aged individuals using menstrual discs across 3 sequential days. Cervicovaginal fluid was processed for cervicovaginal cells, and high-parameter flow cytometry was used to characterize immune populations. We identified large numbers of live, CD45+ leukocytes, as well as distinct populations of T cells and B cells. Within the T cell compartment, activation and suppression status of T cell subsets were consistent with previous studies of the FGT utilizing current approaches, including identification of both tissue-resident and migratory populations. In addition, the T cell population structure was highly conserved across days within individuals but divergent across individuals. Our approach to sample immune cells in the FGT with menstrual discs will decrease barriers to participation and empower longitudinal sampling in future research studies.

SUBMITTER: Peters MQ

PROVIDER: S-EPMC10916362 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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A Noninvasive Method to Sample Immune Cells in the Lower Female Genital Tract Using Menstrual Discs.

Peters M Quinn MQ Domenjo-Vila Eva E Carlson Marc M Armistead Blair B Edlefsen Paul T PT Gasper Melanie M Dabee Smritee S Whidbey Christopher C Jaspan Heather B HB Prlic Martin M Harrington Whitney E WE

ImmunoHorizons 20240201 2

T cells in the human female genital tract (FGT) are key mediators of susceptibility to and protection from infection, including HIV and other sexually transmitted infections. There is a critical need for increased understanding of the distribution and activation of T cell populations in the FGT, but current sampling methods require a healthcare provider and are expensive, limiting the ability to study these populations longitudinally. To address these challenges, we have developed a method to sa ...[more]

PMID: 38386594

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Project description:ObjectiveTo examine the incidence of lower genital tract dysplasia in women after solid organ transplantation, to evaluate risk factors associated with development of dysplasia, and to assess the timeline of disease development.MethodsThis was a retrospective study of female patients who underwent solid organ transplantation at a large-volume tertiary care center between 2000 and 2015. Demographic and clinicopathologic factors were extracted from electronic medical records. Cumulative incidence of lower genital tract dysplasia was calculated, and univariate and multivariable logistic regression were performed to identify risk factors for the development of dysplasia.ResultsAmong 394 female solid organ transplant recipients, the median age was 41 years (interquartile range 29-53). Forty-seven (11.9%; 95% CI 8.8-15.9%) women developed lower genital tract dysplasia over a median follow-up of 7.8 years (interquartile range 4.6-12.9). Thirty-eight (9.6%) developed cervical intraepithelial neoplasia (CIN), with 14 (3.6%) diagnosed with CIN 2 or worse (one was cervical carcinoma). Nineteen (4.8%) developed noncervical lower genital tract dysplasia, including vulvar, vaginal, or anal dysplasia, with 13 (3.3%) diagnosed with high-grade dysplasia or worse (five were lower genital tract carcinoma [three anal, one vulvar, and one vaginal]). Ten (2.5%) developed both cervical and noncervical lower genital tract dysplasia. Black race was significantly associated with developing dysplasia (odds ratio [OR] 2.86; 95% CI 1.33-6.13) as was hydroxychloroquine use (OR 5.95; 95% CI 1.96-18.09). High-grade cervical dysplasia was diagnosed at a median interval of 3.18 years after transplant; noncervical high-grade lower genital tract dysplasia was diagnosed at a median interval of 3.94 years.ConclusionsOne in eight transplant recipients developed lower genital tract dysplasia and approximately half were high-grade dysplasia or cancer. Black race and hydroxychloroquine use were associated with an increased risk of dysplasia. Yearly cervical screening and comprehensive lower genital examination beyond the cervix is indicated in this population.

Project description:Background: Semen induces an immune response at the female genital tract (FGT) to promote conception. It is also the primary vector for HIV transmission to women during condomless sex. Since genital inflammation and immune activation increase HIV susceptibility in women, semen-induced alterations at the FGT may have implications for HIV risk. Here we investigated the impact of semen exposure, as measured by self-reported condom use and Y-chromosome DNA (YcDNA) detection, on biomarkers of female genital inflammation associated with HIV acquisition. Methods: Stored genital specimens were collected biannually (mean 5 visits) from 153 HIV-negative women participating in the CAPRISA 008 tenofovir gel open-label extension trial. YcDNA was detected in cervicovaginal lavage (CVL) pellets by RT-PCR and served as a biomarker of semen exposure within 15 days of genital sampling. Protein concentrations were measured in CVL supernatants by multiplexed ELISA, and the frequency of activated CD4+CCR5+ HIV targets was assessed on cytobrush-derived specimens by flow cytometry. Common sexually transmitted infections (STIs) and bacterial vaginosis (BV)-associated bacteria were measured by PCR. Multivariable linear mixed models were used to assess the relationship between YcDNA detection and biomarkers of inflammation over time. Results: YcDNA was detected at least once in 69% (106/153) of women during the trial (median 2, range 1-5 visits), and was associated with marital status, cohabitation, the frequency of vaginal sex, and Nugent Score. YcDNA detection but not self-reported condom use was associated with elevated concentrations of several cytokines: IL-12p70, IL-10, IFN-γ, IL-13, IP-10, MIG, IL-7, PDGF-BB, SCF, VEGF, β-NGF, and biomarkers of epithelial barrier integrity: MMP-2 and TIMP-4; and with reduced concentrations of IL-18 and MIF. YcDNA detection was not associated with alterations in immune cell frequencies but was related to increased detection of P. bivia (OR = 1.970; CI 1.309-2.965; P = 0.001) at the FGT. Conclusion: YcDNA detection but not self-reported condom use was associated with alterations in cervicovaginal cytokines, BV-associated bacteria, and matrix metalloproteinases, and may have implications for HIV susceptibility in women. This study highlights the discrepancies related to self-reported condom use and the need for routine screening for biomarkers of semen exposure in studies of mucosal immunity to HIV and other STIs.

Project description:The study investigates the causal relationship between gut microbes and female genital tract polyps, exploring the potential mediating role of immune cells via Mendelian randomization (MR) analysis. Our MR study was designed following the STROBE-MR guidelines. We combined data from a large-scale GWAS meta-analysis, including 731 immune profiles and female genital tract polyps, with gut microbiology data sourced from the MiBioGen consortium. Univariate Mendelian randomization was employed to identify gut microbes and immune profiles significantly associated with female genital tract polyps causally. A 2-step MR analysis was utilized to investigate the potential mediating role of immune cells. Furthermore, we utilized the multivariable MR approach based on Bayesian model averaging (MR-BMA) to further assess the prioritization of gut microbiota vs immune characteristics in the development of female genital tract polyps. Through univariate MR analysis, we identified a significant causal link between 12 gut microbiota, 31 immune features, and female genital tract polyps. Four causal pathways involving gut microbiota, immune cells, and polyps were identified among them. MR-BMA analysis indicated marginal inclusion probability (MIP) values exceeding 0.1 for 5 gut microbiota groups: Victivallaceae (model-averaged causal estimate [MACE] = 0.060, MIP = 0.581, P = .0089), Ruminococcus gautreuii (MACE = 0.052, MIP = 0.346, P = .0640), Lachnoclostrium (MACE = 0.0380, MIP = 0.225, P = .1875), Alphaprobacter (MACE = 0.0186, MIP = 0.140, P = .3934), and Fusicatenibacter (MACE = 0.013, MIP = 0.110, P = .5818). Six immune features exhibit high priority, with MIP values exceeding 0.5, including HLA DR on CD33+ HLA DR+ CD14dim (MACE = -0.015, MIP = 0.753, P = .0853), HVEM on naive CD4+ T cell (MACE = 0.024, MIP = 0.737, P = .0053), CD80 on CD62L+ plastic cytoplasmic dendritic cell (MACE = 0.024, MIP = 0.721, P = .0228), CD28 on activated and secret CD4 regulatory T cell (MACE = 0.0054, MIP = 0.706, P = .3245), HLA DR on CD14+ CD16 monocyte (MACE = -0.0003, MIP = 0.520, P = .7927), HLA DR on CD14+ monocyte (MACE = -0.0029, MIP = 0.509, P = .5576). Our research indicates that gut microbiota exerts an independent causal influence on female genital tract polyps, potentially impacting them via various immune cells.

Dataset Information

A Noninvasive Method to Sample Immune Cells in the Lower Female Genital Tract Using Menstrual Discs.

Publications

A Noninvasive Method to Sample Immune Cells in the Lower Female Genital Tract Using Menstrual Discs.

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