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Cervical cytokine network patterns during pregnancy: the role of bacterial vaginosis and geographic ancestry.

ABSTRACT: Few studies have examined the coordinated regulation of the extensive network of cytokines, chemokines, and growth factors involved in the immune response to bacterial vaginosis (BV) during pregnancy. We compared these patterns between women with (BV(+)) and without (BV(-)) bacterial vaginosis and between women of African and of European ancestry. This cohort included 83 Whites (28 BV(+) and 55 BV(-)) and 80 Blacks (41 BV(+) and 39 BV(-)). Pairwise correlations were determined for 28 factors that included cytokines, chemokines, and growth factors. In Whites, there were significantly more correlations involving immunoregulatory cytokines in BV(-) compared with BV(+) women. In Blacks, there were no significant differences in the correlation patterns between BV(+) and BV(-) women. Overall, in BV(-) women, there were no significant differences in the correlation patterns between Whites and Blacks. Conversely, in BV(+) women, Blacks have a stronger correlated response to infection than Whites. This indicates that Whites and Blacks have different correlated immune responses to BV that may at least partially explain the disparity observed in the prevalence of this disease.

SUBMITTER: Ryckman KK

PROVIDER: S-EPMC2688465 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Cervical cytokine network patterns during pregnancy: the role of bacterial vaginosis and geographic ancestry.

Ryckman Kelli K KK Simhan Hyagriv N HN Krohn Marijane A MA Williams Scott M SM

Journal of reproductive immunology 20090101 2

Few studies have examined the coordinated regulation of the extensive network of cytokines, chemokines, and growth factors involved in the immune response to bacterial vaginosis (BV) during pregnancy. We compared these patterns between women with (BV(+)) and without (BV(-)) bacterial vaginosis and between women of African and of European ancestry. This cohort included 83 Whites (28 BV(+) and 55 BV(-)) and 80 Blacks (41 BV(+) and 39 BV(-)). Pairwise correlations were determined for 28 factors tha ...[more]

PMID: 19250684

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Project description:Individuals of African descent in the United States suffer disproportionately from diseases with a metabolic etiology (obesity, metabolic syndrome, and diabetes), and from the pathological consequences of these disorders (hypertension and cardiovascular disease). Using a combination of genetic/genomic and bioinformatics approaches, we identified a large number of genes that were both differentially expressed between American subjects self-identified to be of either African or European ancestry and that also contained single nucleotide polymorphisms that distinguish distantly related ancestral populations. Several of these genes control the metabolism of simple carbohydrates and are direct targets for the SREBP1, a metabolic transcription factor also differentially expressed between our study populations. These data support the concept of stable patterns of gene transcription unique to a geographic ancestral lineage. The coordinated transcriptional adaptation of carbohydrate metabolism to dietary environmental pressures suggests a genetic and transcriptional mechanism for the disproportionate levels of obesity, diabetes, and cardiovascular disease observed in Americans with African ancestry. Keywords: Ancestry-dependent gene expression, functional genomics, personalized medicine, multi-factoral disease, nutrition, diabetes We utilized a “sample x reference” experimental design strategy in which RNA extracted from human peripheral blood mononuclear cells was hybridized to the microarray slide in the presence of labeled Universal Human Reference RNA (UHRR, Stratagene, LaJolla, CA). A total of 161 subjects were used in this analysis. Briefly, five hundred nanograms of total RNA were used for gene expression profiling following reverse transcription and T-7 polymerase-mediated amplification/labeling with Cyanine-5 CTP. Labeled subject cRNA was co-hybridized to Agilent G4112A Whole Human Genome 44K oligonucleotide arrays with equimolar amounts of Cyanine-3 labeled UHRR. Slides were hybridized, washed, and scanned on an Axon 4000b microarray scanner. The data were processed using GenePix Pro 6 software

Project description:BackgroundThe presence of semen in the vagina from unprotected sex may influence the immune and microbial environment of the female genital tract. Inflammatory cytokine concentrations and BV-associated bacteria in female genital secretions may influence HIV risk, although the effect of recent sexual intercourse on incident BV and the cytokine milieu of cervicovaginal secretions has rarely been measured in previous studies. Here, we investigated the extent to which partner semen impacts the cytokine response and incident BV.MethodsAt baseline, we assessed the recency of semen exposure in menstrual cup supernatants by quantifying prostate specific antigen (PSA) levels using ELISA in 248 HIV-uninfected women at high risk for HIV infection. Luminex was used to measure 48 cytokines in menstrual cup supernatants and vaginal swabs to diagnose BV by Nugent score. Point-of-care screening for Chlamydia trachomatis and Neisseria gonorrhoeae was conducted using GeneXpert while OSOM was used for Trichomonas vaginalis detection. Multivariable models, adjusted for age, sexually transmitted infections, BV, current contraception use and condom use, were used to assess the impact of semen exposure on biomarkers of inflammation and BV.ResultsPresence of PSA, indicating recent semen exposure within 48 hours prior to sampling, was observed in menstrual cup supernatants of 17% (43/248) of women. Of these women, 70% (30/43) had self-reported condom use at their last sex act and 84% (36/43) had BV (Nugent score >7). PSA presence was significantly associated with prevalent BV (Relative Risk (RR), 2.609; 95% Confidence Interval (CI), 1.104 - 6.165; p = 0.029). Furthermore, women with detectable PSA had high median concentrations of macrophage inflammatory protein- beta (MIP-1α, p=0.047) and low median concentration of the stem cell growth factor beta (SCGF-β, p=0.038) compared to those without PSA.ConclusionA degree of discordance between self-reports of consistent condom use and PSA positivity was observed. There was also evidence of a relationship between recent semen exposure, BV prevalence and altered cytokine concentrations. These findings suggest that PSA, as a semen biomarker, should be taken into consideration when investigating biological markers in the female genital tract and self-reported condom use in studies on reproductive and sexual health.

Dataset Information

Cervical cytokine network patterns during pregnancy: the role of bacterial vaginosis and geographic ancestry.

Publications

Cervical cytokine network patterns during pregnancy: the role of bacterial vaginosis and geographic ancestry.

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