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Lower genital tract cytokine profiles in South African women living with HIV: influence of mucosal sampling.

ABSTRACT: Measurement of cytokines in the lower female genital tract offer insight into risk for HIV infection and reproductive complications. However, few studies have systematically compared mucosal collection methods or whether collection order matters. We compared longitudinal cytokine profiles in matched genital samples collected from women living with HIV using menstrual cup (MC), endocervical swabs (ECS) and swab-enriched cervicovaginal lavage (eCVL). Samples were collected at enrollment [MC:ECS:eCVL], 3-months (ECS:eCVL:MC) and 6-months (eCVL:MC:ECS) and concentrations of 28 cytokines determined by Luminex. Cytokine clustering was assessed using Principle Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLSDA) and factor analysis. Generally, higher cytokine concentrations were detected in MC samples, followed by ECS and eCVL, irrespective of study visit or sampling order. Factor analysis and PCA identified ECS to be inferior for measuring regulatory cytokines and IP-10 than eCVL or MC. Although concentrations differed, the majority of cytokines correlated between methods. Sampling order influenced cytokine concentrations marginally, and cytokines clustered more strongly by method than study visit. Variance in profiles was lowest in MC, suggesting greater consistency of sampling compared to other methods. We conclude that MC sampling offered advantages over other methods for detecting cytokines in women, with order marginally influencing profiles.

SUBMITTER: Jaumdally SZ

PROVIDER: S-EPMC6093917 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Lower genital tract cytokine profiles in South African women living with HIV: influence of mucosal sampling.

Jaumdally Shameem Z SZ Masson Lindi L Jones Heidi E HE Dabee Smritee S Hoover Donald R DR Gamieldien Hoyam H Langwenya Nontokozo N Myer Landon L Todd Catherine S CS Passmore Jo-Ann S JS

Scientific reports 20180815 1

Measurement of cytokines in the lower female genital tract offer insight into risk for HIV infection and reproductive complications. However, few studies have systematically compared mucosal collection methods or whether collection order matters. We compared longitudinal cytokine profiles in matched genital samples collected from women living with HIV using menstrual cup (MC), endocervical swabs (ECS) and swab-enriched cervicovaginal lavage (eCVL). Samples were collected at enrollment [MC:ECS:eC ...[more]

PMID: 30111808

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Project description:BackgroundWhile prior epidemiologic studies have suggested that injectable progestin-based contraceptive depot medroxyprogesterone acetate (DMPA) use may increase a woman's risk of acquiring HIV, recent data have suggested that DMPA users may be at a similar risk for HIV acquisition as users of the copper intrauterine device and levonorgestrel implant. Use of the etonogestrel Implant (Eng-Implant) is increasing but there are currently no studies evaluating its effect on HIV acquisition risk.ObjectiveEvaluate the potential effect of the Eng-Implant use on HIV acquisition risk by analyzing HIV target cells and cytokine profiles in the lower genital tract and blood of adult premenopausal HIV-negative women using the Eng-Implant.MethodsWe prospectively obtained paired cervicovaginal lavage (CVL) and blood samples at 4 study visits over 16 weeks from women between ages 18-45, with normal menses (22-35 day intervals), HIV uninfected with no recent hormonal contraceptive or copper intrauterine device (IUD) use, no clinical signs of a sexually transmitted infection at enrollment and who were medically eligible to initiate Eng-Implant. Participants attended pre-Eng-Implant study visits (week -2, week 0) with the Eng-Implant inserted at the end of the week 0 study visit and returned for study visits at weeks 12 and 14. Genital tract leukocytes (enriched from CVL) and peripheral blood mononuclear cells (PBMC) from the study visits were evaluated for markers of activation (CD38, HLA-DR), retention (CD103) and trafficking (CCR7) on HIV target cells (CCR5+CD4+ T cells) using multicolor flow cytometry. Cytokines and chemokines in the CVL supernatant and blood plasma were measured in a Luminex assay. We estimated and compared study endpoints among the samples collected before and after contraception initiation with repeated-measures analyses using linear mixed models.ResultsFifteen of 18 women who received an Eng-Implant completed all 4 study visits. The percentage of CD4+ T cells in CVL was not increased after implant placement but the percentage of CD4+ T cells expressing the HIV co-receptor CCR5 did increase after implant placement (p = 0.02). In addition, the percentage of central memory CD4+ T-cells (CCR7+) in CVL increased after implant placement (p = 0.004). The percentage of CVL CD4+, CCR5+ HIV target cells expressing activation markers after implant placement was either reduced (HLA-DR+, p = 0.01) or unchanged (CD38+, p = 0.45). Most CVL cytokine and chemokine concentrations were not significantly different after implant placement except for a higher level of the soluble lymphocyte activation marker (sCD40L; p = 0.04) and lower levels of IL12p70 (p = 0.02) and G-CSF (p<0.001). In systemic blood, none of the changes noted in CVL after implant placement occurred except for decreases in the percentage CD4 T-cells expressing HLA-DR+ T cells (p = 0.006) and G-CSF (p = 0.02).ConclusionsEng-Implant use was associated with a moderate increase in the availability of HIV target cells in the genital tract, however the percentage of these cells that were activated did not increase and there were minimal shifts in the overall immune environment. Given the mixed nature of these findings, it is unclear if these implant-induced changes alter HIV risk.

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.

Dataset Information

Lower genital tract cytokine profiles in South African women living with HIV: influence of mucosal sampling.

Publications

Lower genital tract cytokine profiles in South African women living with HIV: influence of mucosal sampling.

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