Cervicovaginal levels of human beta defensins during bacterial vaginosis

Abstract

Aims To compare the cervicovaginal levels of human beta defensin (hBD)-1, 2 and 3 of women according to the status of Nugent-defined bacterial vaginosis (BV). Methods A total of 634 women of reproductive age were included in the study. Participants were equally distributed in two groups: according to the classification of vaginal smears according to Nugent criteria in normal (scores 0 to 3) and BV (scores ≥7). Cervicovaginal fluid samples were used for measurements of hBDs1, 2 and 3 levels by enzyme-linked immunosorbent assay (ELISA). Levels of each hBD were compared between the two study groups using Mann-Whitney test, with p-value <0.05 considered as significant. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated for sociodemographic variables and hBD1-3 levels associated with BV a multivariable analysis. Correlation between Nugent score and measured levels of hBDs1-3 were calculated using Spearman’s test. Results Cervicovaginal fluids from women with BV showed lower levels of hBD-1 [median 2,400.00 pg/mL (0–27,800.00); p<0.0001], hBD-2 [5,600.00 pg/mL (0–45,800.00); p<0.0001] and hBD-3 [1,600.00 pg/mL (0–81,700.00); p = 0.012] when compared to optimal microbiota [hBD-1: [median 3,400.00 pg/mL (0–35,600.00), hBD-2: 12,300.00 pg/mL (0–95,300.00) and hBD-3: 3,000.00 pg/mL (0–64,300.00), respectively]. Multivariable analysis showed that lower levels of hBD-1 (OR: 2.05; 95% CI: 1.46–2.87), hBD-2 (OR: 1.85; 95% CI: 1.32–2.60) and hBD-3 (OR: 1.90; 95% CI: 1.37–2.64) were independently associated BV. Significant negative correlations were observed between Nugent scores and cervicovaginal levels of hBD-1 (Spearman’s rho = -0.2118; p = 0.0001) and hBD-2 (*Spearman’s rho = -0.2117; p = 0.0001). Conclusions Bacterial vaginosis is associated with lower cervicovaginal levels of hBDs1-3 in reproductive-aged women.

Cervicovaginal Microbial–Immune State and Group B Streptococcus Colonization in Pregnancy

“…Several recent studies have demonstrated an association between low levels of β-defensin-2 and numerous obstetric and gynecologic pathologies, including preterm birth, bacterial vaginosis, lichen sclerosis, sexually transmitted infections. 3,12,28,29 In regards to GBS specifically, prior in vitro work by Castro-Leyva et al demonstrated that when incubated with S. agalactiae, choriodecidual cells increased production of β-defensin-2. 30 Boldenow et al showed increased β-defensin-2 production by GBS-exposed amnion cells and also found that in bacterial culture, β-defensin-2 decreased GBS viability in a concentration-dependent manner.…”

“…7,8 Furthermore, recent works have demonstrated that antimicrobial peptide β-defensin-2 is associated with nonoptimal CV microbiota as well as bacterial vaginosis and sexually transmitted infections, but the impact of β-defensin-2 on GBS colonization in pregnancy has not yet been examined. 3,5,12,13 Therefore, we sought to determine whether the CV microbiota was associated with GBS RV colonization in pregnancy. We examined the relationship between GBS RV colonization and various characteristics of the CV microbiome at multiple time points throughout pregnancy.…”

Defensins: defenders of human reproductive health

“…Clinical studies have found defensin deficiency in vaginal lavage fluids of women with BV. Effective treatment normalizes defensin levels in BV, suggesting that abnormal defensin levels are a consequence of G. vaginalis infection ( Balu et al , 2002 ; Valore et al , 2006 ; Fan et al , 2008 ; Libby et al , 2008 ; Xu et al , 2008 ; Mitchell et al , 2013 ; Noda-Nicolau et al , 2021 ). However, in vitro experiments showed that G. vaginalis infection could induce HBD1–3 secretion in human chorioamnion ( Zaga-Clavellina et al , 2012a ).…”

“…Inconsistent changes in defensin levels were found in lavage fluids from patients with G. vaginalis infection, for instance, decreased levels of HBD1–3 in the cervix of childbearing age women ( Noda-Nicolau et al , 2021 ), increased HNP1–3 concentrations in vaginal fluid of pregnant women ( Balu et al , 2002 ; Xu et al , 2008 ) and low HBD3 concentrations in vaginal fluid of African American pregnant women ( Mitchell et al , 2013 ). In postmenopausal women, HBD1 levels were significantly decreased, and HBD2 and HBD3 levels were significantly increased ( Brunner et al , 2021 ).…”