Obstetric outcomes in women with vulvodynia or vaginismus.

PURPOSE: Vulvodynia and vaginismus are common chronic vulvar pain disorders for which there is a paucity of literature on pregnancy outcomes of affected women. The study objective was to evaluate the associations between vulvodynia and vaginismus and obstetric outcomes. METHODS: We performed a retrospective cohort study including all birth-related admissions from 1999 to October 2015 extracted from the Healthcare Cost and Utilization Project-National Inpatient Sample from the United States. Women with vulvodynia or vaginismus were identified using the appropriate ICD-9 codes. Multivariate logistic regression models, adjusted for baseline maternal characteristics, were performed to evaluate the effect of vulvodynia and vaginismus on obstetrical and neonatal outcomes. RESULTS: A total of 879 obstetrical patients with vulvodynia or vaginismus were identified in our cohort of 13,792,544 patients admitted for delivery in US hospitals between 1999 and 2015, leading to an overall prevalence of 6 cases per 100,000 births. Between 1999 and 2015, the annual prevalence of vulvodynia or vaginismus rose from 2 to 16 cases per 100,000. Vulvodynia and vaginismus were associated with increased risks of eclampsia, chorioamnionitis, post-term pregnancy, cesarean delivery, instrumental vaginal delivery, blood transfusions, prolonged hospital stays, congenital anomalies and intrauterine growth restriction. CONCLUSION: Vulvodynia and vaginismus in pregnancy appears underreported in pregnancy compared to reported population rates. Prevalence of reporting seems to have increased in the last decades and is associated with increased risks of maternal and newborn morbidities. Obstetrical caregivers should be aware of the underreporting of these conditions and the associated adverse effects when counseling obstetrical patients.

Antibody-Induced Internalization of HIV-1 Env Proteins Limits Surface Expression of the Closed Conformation of Env.

To minimize immune responses against infected cells, HIV-1 limits the surface expression of its envelope glycoprotein (Env). Here, we demonstrate that this mechanism is specific for the Env conformation and affects the efficiency of antibody-dependent cellular cytotoxicity (ADCC). Using flow cytometry and confocal microscopy, we show that broadly neutralizing antibodies (bNAbs) targeting the "closed" conformation of Env induce its internalization from the surface. In contrast, non-neutralizing antibodies (nNAbs) are displayed on the cell surface for prolonged period of times. The bNAb-induced Env internalization can be decreased by blocking dynamin function, which translates into higher susceptibilities of infected cells to ADCC. Our results suggest that antibody-mediated Env internalization is a mechanism used by HIV-1 to evade immune responses against the "closed" conformation of Env expressed on HIV-1-infected cells.IMPORTANCE HIV-1 has evolved to acquire several strategies to limit the exposure of its envelope glycoproteins (Env) on the surface of infected cells. In this study, we show that antibody-induced Env internalization is conformation specific and reduces the susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). Thus, a better understanding of this mechanism might help develop antibodies with improved capacities to mediate ADCC.

Two Families of Env Antibodies Efficiently Engage Fc-Gamma Receptors and Eliminate HIV-1-Infected Cells.

HIV-1 conceals epitopes of its envelope glycoproteins (Env) recognized by antibody (Ab)-dependent cellular cytotoxicity (ADCC)-mediating antibodies. These Abs, including anti-coreceptor binding site (CoRBS) and anti-cluster A antibodies, preferentially recognize Env in its "open" conformation. The binding of anti-CoRBS Abs has been shown to induce conformational changes that further open Env, allowing interaction of anti-cluster A antibodies. We explored the possibility that CoRBS Abs synergize with anti-cluster A Abs to engage Fc-gamma receptors to mediate ADCC. We found that binding of anti-CoRBS and anti-cluster A Abs to the same gp120 is required for interaction with soluble dimeric FcγRIIIa in enzyme-linked immunosorbent assays (ELISAs). We also found that Fc regions of both Abs are required to optimally engage FcγRIIIa and mediate robust ADCC. Taken together, our results indicate that these two families of Abs act together in a sequential and synergistic fashion to promote FcγRIIIa engagement and ADCC.IMPORTANCE The "open" CD4-bound conformation of HIV-1 envelope glycoproteins is the primary target of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies present in HIV-positive (HIV+) sera, such as anti-coreceptor binding site and anti-cluster A antibodies. Here we report that the binding of these two families of antibodies is required to engage FcγRIIIa and mediate ADCC.