Search

BackgroundIn malaria-endemic areas, the first exposure to malaria antigens often occurs in utero when the fetal immune system is poised towards the development of tolerance. Children exposed to placental malaria have an increased risk of clinical malaria in the first few years of life compared to unexposed children. Recent work has suggested the potential of pregnancy-associated malaria to induce immune tolerance in children living in malaria-endemic areas. A study was completed to evaluate the effect of malaria exposure during pregnancy on fetal immune tolerance and effector responses.MethodsUsing cord blood samples from a cohort of mother-infant pairs followed from early in pregnancy until delivery, flow cytometry analysis was completed to assess the relationship between pregnancy-associated malaria and fetal cord blood CD4 and dendritic cell phenotypes.ResultsCord blood FoxP3+ Treg counts were higher in infants born to mothers with Plasmodium parasitaemia early in pregnancy (12-20 weeks of gestation; p = 0.048), but there was no association between Treg counts and the presence of parasites in the placenta at the time of delivery (by loop-mediated isothermal amplification (LAMP); p = 0.810). In contrast, higher frequencies of activated CD4 T cells (CD25+FoxP3-CD127+) were observed in the cord blood of neonates with active placental Plasmodium infection at the time of delivery (p = 0.035). This population exhibited evidence of effector memory differentiation, suggesting priming of effector T cells in utero. Lastly, myeloid dendritic cells were higher in the cord blood of infants with histopathologic evidence of placental malaria (p

Transplantation-related mortality (TRM) is high after HLA-mismatched umbilical cord blood (UCB) transplantation (UCBT). In utero, exposure to noninherited maternal antigen (NIMA) is recognized by the fetus, which induces T regulator cells to that haplotype. It is plausible that UCBTs in which recipients are matched to donor NIMAs may alleviate some of the excess mortality associated with this treatment. To explore this concept, we used marginal matched-pair Cox regression analysis to compare outcomes in 48 NIMA-matched UCBTs (ie, the NIMA of the donor UCB unit matched to the patient) and in 116 non-NIMA-matched UCBTs. All patients had a hematologic malignancy and received a single UCB unit. Cases and controls were matched on age, disease, disease status, transplantation-conditioning regimen, HLA match, and infused cell dose. TRM was lower after NIMA-matched UCBTs compared with NIMA-mismatched UCBTs (relative risk, 0.48; P = .05; 18% versus 32% at 5 years posttransplantation). Consequently, overall survival was higher after NIMA-matched UCBT. The 5-year probability of overall survival was 55% after NIMA-matched UCBTs versus 38% after NIMA-mismatched UCBTs (P = .04). When faced with the choice of multiple HLA-mismatched UCB units containing adequate cell doses, selecting an NIMA-matched UCB unit may improve survival after mismatched UCBT.

Bovine perinatal mortality due to infection may result either from the direct effects of intrauterine infection and/or the fetal response to such infection, leading to the fetal inflammatory response syndrome (FIRS). Both intrauterine infection and FIRS, which causes multi-organ damage and involution of immune organs, compromise fetal survivability, sometimes fatally. Organ injury associated with FIRS may, in addition to causing fetal mortality, irreversibly compromise extrauterine adaptation of the neonate, a recognized problem in human fetuses. Diagnosis of intrauterine infection and of FIRS requires related, but independent analytical approaches. In addition to detection of pathogens, the immune and inflammatory responses of the bovine fetus may be utilized to diagnose intrauterine infection. This can be done by detection of specific changes in internal organs and the measurement of antibodies and/or elements of the acute phase reaction. Currently our ability to diagnose FIRS in bovine fetuses and neonates is limited to research studies. This review focuses on both the fetomaternal response to infection and diagnostic methods which rely on the response of the fetus to infection and inflammatory changes, as well other methods which may improve diagnosis of intrauterine infection in cases of bovine perinatal mortality.

Abstract Background In malaria-endemic areas, the first exposure to malaria antigens often occurs in utero when the fetal immune system is poised towards the development of tolerance. Children exposed to placental malaria have an increased risk of clinical malaria in the first few years of life compared to unexposed children. Recent work has suggested the potential of pregnancy-associated malaria to induce immune tolerance in children living in malaria-endemic areas. A study was completed to evaluate the effect of malaria exposure during pregnancy on fetal immune tolerance and effector responses. Methods Using cord blood samples from a cohort of mother-infant pairs followed from early in pregnancy until delivery, flow cytometry analysis was completed to assess the relationship between pregnancy-associated malaria and fetal cord blood CD4 and dendritic cell phenotypes. Results Cord blood FoxP3+ Treg counts were higher in infants born to mothers with Plasmodium parasitaemia early in pregnancy (12–20 weeks of gestation; p = 0.048), but there was no association between Treg counts and the presence of parasites in the placenta at the time of delivery (by loop-mediated isothermal amplification (LAMP); p = 0.810). In contrast, higher frequencies of activated CD4 T cells (CD25+FoxP3−CD127+) were observed in the cord blood of neonates with active placental Plasmodium infection at the time of delivery (p = 0.035). This population exhibited evidence of effector memory differentiation, suggesting priming of effector T cells in utero. Lastly, myeloid dendritic cells were higher in the cord blood of infants with histopathologic evidence of placental malaria (p

Objective: The purpose of this study was to determine the relationship between fetal inflammatory and immune responses to oral pathogens and risk for preterm birth. Study design: Six hundred and forty umbilical cord blood specimens were prospectively collected. Cord serum levels of C-reactive protein, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, Prostaglandin E2, and 8-isoprostane were determined by enzyme-linked immunosorbent assay and categorized as > median (high) versus ⩽ median (low). Presence of fetal immunoglobulin M (IgM) antibody against oral pathogens was determined by checkerboard immunoblot assay; detection of ⩾1 oral pathogen specific antibody was categorized as positive. Preterm birth was defined as spontaneous delivery at <35 weeks. Chi-square analysis was used to determine association between cord serum mediator or IgM category and preterm birth. Odds ratios (OR) for preterm birth were calculated, stratified by mediator and IgM category. Results: Of 640 births, 48 (7.5%) delivered preterm. Preterm birth rates were higher if categorized as high versus low 8-isoprostane or TNF-α (23 vs 5%, P < .001 and 10 vs 4%, P < .01, respectively). Preterm birth rates were also higher if categorized as IgM positive versus negative (10.6 vs 5.8%, P = .04). The joint effects of fetal IgM seropositivity, detectable C-reactive protein, or high 8-isoprostane, PGE2, or TNF-α resulted in significantly increased risk for preterm birth (adjusted OR [95% CI]: 6.0 [2.2-16.5], 4.3 [1.6-11.5], 4.1 [1.5-11.6], and 7.6 [2.3-20.8], respectively). Conclusion: Fetal exposure to oral pathogens evidenced by an IgM response is associated with preterm birth, and the risk for preterm birth is greatest among fetuses that also demonstrate an inflammatory response. [ABSTRACT FROM AUTHOR]

Simple Summary: Bovine perinatal mortality (death of the fetus or calf before, during, or within 48 h of calving at full term (≥260 days) may be caused by noninfectious and infectious causes. Although infectious causes of fetal mortality are diagnosed less frequently, infection in utero may also compromise the development of the fetus without causing death. This review presents fetomaternal responses to infection and the changes which can be observed in such cases. Response to infection, especially the concentration of immunoglobulins and some acute-phase proteins, may be used for diagnostic purposes. Some changes in internal organs may also be used as an indicator of infection in utero. However, in all cases (except pathogen-specific antibody response) non-pathogen-specific responses do not aid in pathogen-specific diagnosis of the cause of calf death. But, nonspecific markers of in utero infection may allow us to assign the cause of fetal mortality to infection and thus increase our overall diagnosis rate, particularly in cases of the "unexplained stillbirth". Bovine perinatal mortality due to infection may result either from the direct effects of intrauterine infection and/or the fetal response to such infection, leading to the fetal inflammatory response syndrome (FIRS). Both intrauterine infection and FIRS, which causes multi-organ damage and involution of immune organs, compromise fetal survivability, sometimes fatally. Organ injury associated with FIRS may, in addition to causing fetal mortality, irreversibly compromise extrauterine adaptation of the neonate, a recognized problem in human fetuses. Diagnosis of intrauterine infection and of FIRS requires related, but independent analytical approaches. In addition to detection of pathogens, the immune and inflammatory responses of the bovine fetus may be utilized to diagnose intrauterine infection. This can be done by detection of specific changes in internal organs and the measurement of antibodies and/or elements of the acute phase reaction. Currently our ability to diagnose FIRS in bovine fetuses and neonates is limited to research studies. This review focuses on both the fetomaternal response to infection and diagnostic methods which rely on the response of the fetus to infection and inflammatory changes, as well other methods which may improve diagnosis of intrauterine infection in cases of bovine perinatal mortality. [ABSTRACT FROM AUTHOR]

Foetal response to hepatitis B viral infection is still unknown. The mechanisms of persistent infection that occurs more often in mother-to-child transmission than adult transmission are also unclear. Various aspects of the environmental factors that accelerate or inhibit infection and the cytokine responses are associated with the persistence of infection. Several studies showed that the cytokine poor immune response in immaturity causes the persistence of the infection. However, some reports suggested that a mature immune response was the cause of this persistent infection. This review comprehensively summarized the reports from in vitro , in vivo as well as clinical reports regarding the responses of the foetuses of hepatitis B infected mothers to the micro-organism. The mechanism of more opportunities to be persistently infected via the mother-to-child transmission route is also summarized and discussed. Since there are limited clinical reports at this time, this review will provide evidence for future studies regarding the intrauterine infection mechanism and foetal response to hepatitis B virus to elucidate the mechanisms responsible for mother-to-child transmission. This understanding may lead to effective interventions to control mother-to-child hepatitis B infection in the future.