Maternal immunization with ovalbumin prevents neonatal allergy development and up-regulates inhibitory receptor Fc gamma RIIB expression on B cells.

BACKGROUND: Preconception allergen immunization prevents neonatal allergen sensitization in mice by a complex interaction between regulatory cells/factors and antibodies. The present study assessed the influence of maternal immunization with ovalbumin (OVA) on the immune response of 3 day-old and 3 week-old offspring immunized or non-immunized with OVA and evaluated the effect of IgG treatment during fetal development or neonatal period. RESULTS: Maternal immunization with OVA showed increased levels of Fc gamma RIIb expression in splenic B cells of neonates, which were maintained for up to 3 weeks and not affected by additional postnatal OVA immunization. Maternal immunization also exerted a down-modulatory effect on both IL-4 and IFN-gamma-secreting T cells and IL-4 and IL-12- secreting B cells. Furthermore, immunized neonates from immunized mothers showed a marked inhibition of antigen-specific IgE Ab production and lowered Th2/Th1 cytokine levels, whereas displaying enhanced Fc gamma RIIb expression on B cells. These offspring also showed reduced antigen-specific proliferative response and lowered B cell responsiveness. Moreover, in vitro evaluation revealed an impairment of B cell activation upon engagement of B cell antigen receptor by IgG from OVA-immunized mice. Finally, in vivo IgG transference during pregnancy or breastfeeding revealed that maternal Ab transference was able to increase regulatory cytokines, such as IL-10, in the prenatal stage; yet only the postnatal treatment prevented neonatal sensitization. None of the IgG treatments induced immunological changes in the offspring, as it was observed for those from OVA-immunized mothers. CONCLUSION: Maternal immunization upregulates the inhibitory Fc gamma RIIb expression on offspring B cells, avoiding skewed Th2 response and development of allergy. These findings contribute to the advancement of prophylactic strategies to prevent allergic diseases in early life.

CpG-induced Th1-type response in the downmodulation of early development of allergy and inhibition of B7 expression on T cells of newborn mice.

INTRODUCTION: Several differences have been described between neonatal and adult immune responses. The predisposition in early life to Th2-type response or tolerance makes it a susceptible period for infections and allergic sensitization. OBJECTIVE: The aim of this work was to evaluate the effects of CpG-containing oligodeoxynucleotides on neonatal and adult immunization with ovalbumin and Blomia tropicalis extract and compare the CpG effects on B and T cells of neonatal and adult mice. RESULTS AND DISCUSSION: Mice that received CpG showed reduced immunoglobulin E (IgE) antibody production in both neonatal and adult periods, in parallel to increased IgG2a antibody levels. We observed that spleen cells of mice that received CpG in early life produced increased amounts of interferon-gamma upon anti-CD3 stimulation. Negative regulation of IgE response was more pronounced in adult than neonate mice; further, CpG decreased anaphylactic antiovalbumin IgG1 only in adults. Also, an upregulation of toll-like receptor 9 expression was detected in adult B cells, but not in neonatal, upon CpG stimuli. Neonatal B cells showed enhanced interleukin (IL)-10 expression and decreased IL-6 levels than adult B cells in response to CpG. When we analyzed in vitro activation of CD4+ T cells, an increased expression of B7 molecules on T cells in neonates was suppressed by CpG. CONCLUSION: Altogether, we verified qualitative and quantitative evidences regarding CpG effect on neonatal and adult allergens immunizations, which points to the importance of understanding neonatal immune system to establish immunomodulatory strategies for prevention of allergic diseases.

Association between the timing of maternal vaccination and newborns' anti-pertussis toxin antibody levels.

BACKGROUND: Pertussis remains an important global public health concern, despite the presence of extensive immunization programs. Incidence and severity of pertussis are typically higher in neonates and young infants. As a strategy to protect these young infants, maternal vaccination with Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) has been recommended in Brazil. The objective of this study was to evaluate the effects of Tdap vaccination during pregnancy on the anti-pertussis toxin (PT) IgG response in mothers and their infants at birth. MATERIAL AND METHODS: Maternal and cord blood samples were collected from vaccinated (n = 243) and unvaccinated (n = 75) pregnant women, at the time of delivery, from July 2015 to August 2016 in São Paulo, Brazil. Anti-PT IgG antibodies were quantified by Enzyme-Linked Immunosorbent Assay (ELISA) and geometric mean concentrations (GMC) were calculated. Relationship between timing of vaccination and antibody concentrations were evaluated. RESULTS: Maternal and cord blood GMCs among the vaccinated group were 5.4 and 5.6 fold higher [66.5 International Units (IU)/mL and 89.8 IU/mL] compared to the unvaccinated group (12.4 IU/mL and 16.1 IU/mL), respectively (p < 0.001). Higher anti-PT IgG GMCs were observed when vaccination occurred ≥60 days before delivery compared to <60 days, suggesting that vaccination early in the third trimester may be more effective than later in pregnancy. CONCLUSION: Tdap maternal vaccination results in significantly higher anti-PT IgG in newborn infants and supports the current recommendation of the Brazilian Immunization Program.

The effectiveness of maternal pertussis vaccination in protecting newborn infants in Brazil: A case-control study.

INTRODUCTION: In 2014, the Brazilian Ministry of Health (MoH) recommended Tdap to pregnant women in response to a significant increase in the incidence of pertussis among infants. The present study assessed the effectiveness of maternal immunization in preventing pertussis in infants. METHODS: An unmatched case-control study was undertaken in São Paulo State, Brazil from February 2015 to July 2016. Cases were infants aged <8 weeks at onset of pertussis reported to the Surveillance System and confirmed by real-time polymerase chain reaction or culture. Four to six healthy infants were selected as controls per case from birth certificates in the Information System on Live Births database. General characteristics and mother's vaccination status were compared between cases and controls. The vaccine effectiveness (VE) was calculated as 1 - odds ratio (OR). For the adjusted VE, the OR was calculated using logistic regression analysis. RESULTS: Forty-two cases and 248 controls were enrolled in the study. Mothers of 8 cases (19.1%) and 143 controls (57.4%) were vaccinated during pregnancy, resulting in an unadjusted VE of 82.6% (95% confidence interval [CI], 60.8-92.3%). The VE was unchanged after adjusting for maternal age and monthly household income. CONCLUSION: Maternal pertussis vaccination during pregnancy was effective in protecting infants aged <8 weeks from pertussis.

The Relationship between Maternal Plasma Leptin and Adiponectin Concentrations and Newborn Adiposity.

Increased maternal blood concentrations of leptin and decreased adiponectin levels, which are common disturbances in obesity, may be involved in offspring adiposity by programming fetal adipose tissue development. The aim of this study was to assess the relationship between maternal leptin and adiponectin concentrations and newborn adiposity. This was a cross-sectional study involving 210 healthy mother-newborn pairs from a public maternity hospital in São Paulo, Brazil. Maternal blood samples were collected after delivery and leptin and adiponectin concentrations were measured by enzyme-linked immunosorbent assay. Newborn body composition was estimated by air displacement plethysmography. The association between maternal leptin and adiponectin concentrations and newborn adiposity (fat mass percentage, FM%) was evaluated by multiple linear regression, controlling for maternal age, socioeconomic status, parity, pre-pregnancy body mass index (BMI), weight gain, gestational age, and newborn age at the time of measurement. No relationship was found between maternal leptin and FM% of male or female newborn infants. Maternal adiponectin (p = 0.001) and pre-pregnancy BMI (p < 0.001; adj. R² = 0.19) were positively associated with FM% of newborn males, indicating that maternal adiponectin is involved in fetal fat deposition in a sex-specific manner. Large-scale epidemiological, longitudinal studies are necessary to confirm our results.

Long-term anergy in orally tolerized mice is linked to decreased B7.2 expression on B cells.

Durable antigen (Ag)-specific T- and B-cell anergy induced by oral tolerance is an attractive strategy for immunotherapy of allergic diseases. Here, we address the lasting effect of oral tolerance induction in naïve or primed mice to ovalbumin (OVA) on antibody production. Single feeding with OVA prior to immunization or double feeding, before and after Ag priming, in A/Sn mice, induced a long-lasting suppression of IgE, IgG1 and IgG2a responses up to 8 months after immunization. In contrast, primed-fed mice had transient IgE inhibition. Naive and double-treated mice showed marked Ag-specific unresponsiveness and scarce cytokines production. Inhibition of IL-2 and IFN-gamma secretion in naïve-fed mice were restored in the presence of anti-CD28 mAb plus Ag stimulation. The durable inhibition of Ab production in OVA-fed mice was related to the persistent decrease of B7.2 expression on B cells. Ag feeding in naive and primed status may be a prophylactic measure to avoid later Ag sensitization.

Staphylococcal enterotoxin B induces specific IgG4 and IgE antibody serum levels in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic recurrent inflammatory disease, with prevalence of about 10-20% in children and 1-3% in adults. Staphylococcus aureus is present in 80-100% of skin from atopic patients and is related to worsening of the disease by the action of enterotoxins. The aim of this study was to evaluate the profile of anti-Staphylococcus aureus enterotoxin B (SEB) antibody isotypes and IgG subclass levels in adult AD. METHODS: We selected 38 patients with AD, diagnosed by Hanifin and Rajka's criteria, aged between 18 and 65, and 26 healthy controls (HC). The severity of the disease was established according to the Eczema Area and Severity Index and patients graded as mild (28%), moderate (58%), and severe (14%). Sera were assessed for IgG subclasses, IgA, IgM, and IgE against SEB by ELISA. RESULTS: Elevated circulating IgE and IgG4 anti-SEB antibody levels associated with decreased IgA and IgM levels were detected in patients with AD, when compared to HC individuals. The severity of AD was related to low IgG1 and IgG3 levels and a high IgE antibody response to SEB. Interestingly, absence of IgG4 response to SEB was lower in patients with AD (2.63%), when compared to controls (34.6%), while a similar absence was detected for IgG1 and IgE antibodies (AD, 23.3 and 18.4% vs. HC, 38.5 and 19.2%). CONCLUSION: Our findings evidenced a contributing role for IgG4 and IgE antibodies in AD pathogenesis, which are triggered by staphylococcal superantigens.

Serodiagnosis as adjunct assay for pertussis infection in São Paulo, Brazil.

Pertussis remains an important public health problem in many countries despite extensive immunization. Cultures and real-time PCR (RT-PCR) assays are the recommended pertussis diagnostic tests, but they lack sensitivity at the later stage of the disease. This study introduces the IgG anti-pertussis toxin enzyme-linked immunosorbent assay (PT ELISA) in our routine diagnosis to improve disease burden estimation. Serum samples and nasopharyngeal swabs (n = 503) were collected at the same time from patients presenting with cough illness suspected of being pertussis and tested by the PT ELISA and culture and/or RT-PCR, respectively. Patients were separated into three age groups: group 1, <1 year (n = 260; mean age, 3 months), group 2, 1 to 6 years (n = 81; mean age, 3 years), and group 3, ≥7 years (n = 162; mean age, 26 years). The times (means) from cough onset to specimen collection were 16, 24, and 26 days, respectively. In group 1, 83 (82.2%) of 101 positive cases were positive for pertussis by culture/RT-PCR, while 40 (39.6%) tested positive by PT ELISA. In group 2, 6 (19.4%) of 31 positive cases were culture/RT-PCR positive, and 29 (93.6%) were seropositive. In group 3, 13 (13.8%) of 94 positive cases were positive by culture/RT-PCR and 91 (96.8%) were positive by serology. Culture/RT-PCR detected more cases of pertussis in infants (P < 0.0001), whereas the PT ELISA detected more cases in adolescents and adults (P < 0.0001). The timing between cough onset and specimen collection or recent vaccination may have partially affected our results. Serology is a suitable, cost-effective, and complementary pertussis diagnostic tool, especially among older children, adolescents, and adults during the later disease phase.

Maternal-fetal interaction: preconception immunization in mice prevents neonatal sensitization induced by allergen exposure during pregnancy and breastfeeding.

Allergen exclusion measures during pregnancy and lactation have been given consideration in studies of primary allergy prevention but complete avoidance of mother/neonatal allergen exposure has proven to be a difficult procedure. To evaluate a strategy to prevent allergen sensitization in early life in mice, we first established a neonatal model with ovalbumin sensitization through maternal allergen exposure during pregnancy or breastfeeding. The modulatory potential of preconception immunization was investigated on the neonatal development of subsequent allergic responses to maternal allergen exposure. Herein, we demonstrate that immunized mothers exposed to antigen during pregnancy or breastfeeding underwent intense vertical transmission of antibodies, including immunoglobulin G (IgG) in complex with ovalbumin and IgG1 antibody with anaphylactic function. It was further shown that maternal immunization efficiently decreased the passage of free antigens through breastfeeding and inhibited the enhanced IgE antibody response after postnatal antigen exposure. In addition, antenatal immunization decreased the antigen-specific proliferative response of immunized neonates, in parallel with profound downmodulatory effects on both the activation and differentiation of T and B cells after a non-specific stimulus and cytokine production. These findings showed that early life sensitization, subsequent to maternal allergen exposure during both the prenatal and postnatal periods, could be avoided by preventive vaccination of the mother.

Trombose traumática da artéria carótida interna cervical / Traumatic thrombosis of the internal carotid artery

A artéria carótida interna pode ser lesada na regiäo cervical por contusöes diretas no pescoço, ou por estiramento sobre as massas laterais do atlas e axis, quando o pescoço é hiperextendido, seguindo-se rotaçäo e desvio lateral da cabeça, contralateral ao lado do trauma. O diagnóstico deve ser feito antes que ocorra trombose total, pois assim a reparaçäo cirúrgica pode ser realizada, evitando graves seqüelas neurológicas ou a morte. Nesta nossa casuística de 6 pacientes, 2 se apresentaram com hemiparesias, 1 com ataque isquêmico transitório, 2 com sinais neurológicos graves e 1 faleceu. Todos os casos foram diagnosticados por arteriografia cerebral. A cirurgia foi realizada em 3 pacientes, com sucesso em 2