Inhibition of IL-10 Production by Maternal Antibodies against Group B Streptococcus GAPDH Confers Immunity to Offspring by Favoring Neutrophil Recruitment

Group B Streptococcus (GBS) is the leading cause of neonatal pneumonia, septicemia, and meningitis. We have previously shown that in adult mice GBS glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extracellular virulence factor that induces production of the immunosuppressive cytokine interleukin-10 (IL-10) by the host early upon bacterial infection. Here, we investigate whether immunity to neonatal GBS infection could be achieved through maternal vaccination against bacterial GAPDH. Female BALB/c mice were immunized with rGAPDH and the progeny was infected with a lethal inoculum of GBS strains. Neonatal mice born from mothers immunized with rGAPDH were protected against infection with GBS strains, including the ST-17 highly virulent clone. A similar protective effect was observed in newborns passively immunized with anti-rGAPDH IgG antibodies, or F(ab')2 fragments, indicating that protection achieved with rGAPDH vaccination is independent of opsonophagocytic killing of bacteria. Protection against lethal GBS infection through rGAPDH maternal vaccination was due to neutralization of IL-10 production soon after infection. Consequently, IL-10 deficient (IL-10−/−) mice pups were as resistant to GBS infection as pups born from vaccinated mothers. We observed that protection was correlated with increased neutrophil trafficking to infected organs. Thus, anti-rGAPDH or anti-IL-10R treatment of mice pups before GBS infection resulted in increased neutrophil numbers and lower bacterial load in infected organs, as compared to newborn mice treated with the respective control antibodies. We showed that mothers immunized with rGAPDH produce neutralizing antibodies that are sufficient to decrease IL-10 production and induce neutrophil recruitment into infected tissues in newborn mice. These results uncover a novel mechanism for GBS virulence in a neonatal host that could be neutralized by vaccination or immunotherapy. As GBS GAPDH is a structurally conserved enzyme that is metabolically essential for bacterial growth in media containing glucose as the sole carbon source (i.e., the blood), this protein constitutes a powerful candidate for the development of a human vaccine against this pathogen

Estimation of early life endogenous surfactant pool and CPAP failure in preterm neonates with RDS

Abstract Background It is not known if the endogenous surfactant pool available early in life is associated with the RDS clinical course in preterm neonates treated with CPAP. We aim to clarify the clinical factors affecting surfactant pool in preterm neonates and study its association with CPAP failure. Methods Prospective, pragmatic, blind, cohort study. Gastric aspirates were obtained (within the first 6 h of life and before the first feeding) from 125 preterm neonates with RDS. Surfactant pool was measured by postnatal automated lamellar body count based on impedancemetry, without any pre-analytical treatment. A formal respiratory care protocol based on European guidelines was applied. Clinical data and perinatal risk factors influencing RDS severity or lamellar body count were real-time recorded. Investigators performing lamellar body count were blind to the clinical data and LBC was not used in clinical practice. Results Multivariate analysis showed gestational age to be the only factor significantly associated with lamellar body count (standardized β:0.233;p = 0.023). Lamellar body count was significantly higher in neonates with CPAP success (43.500 [23.750–93.750]bodies/μL), than in those failing CPAP (20.500 [12.250–49.750] bodies/μL;p = 0.0003).LBC had a moderate reliability to detect CPAP failure (AUC: 0.703 (0.615–0.781);p < 0.0001; best cut-off: ≤30,000 bodies/μL). Upon adjustment for possible confounders, neither lamellar body count, nor its interaction factor with gestational age resulted associated with CPAP failure. Conclusions Early postnatal lamellar body count on gastric aspirates in CPAP-treated preterm neonates with RDS is significantly influenced only by gestational age. Lamellar bodies are not associated with CPAP failure. Thus, the endogenous surfactant pool available early in life only has a moderate reliability to predict CPAP failure

A noninvasive surfactant adsorption test predicting the need for surfactant therapy in preterm infants treated with continuous positive airway pressure

Objective: To determine the diagnostic accuracy of the surfactant adsorption test (SAT) as a predictor for the need for surfactant replacement therapy in neonates with respiratory distress syndrome (RDS). Study design Amniotic fluid samples were collected from 41 preterm neonates with RDS treated with continuous positive airway pressure (CPAP) and 15 healthy control term neonates. Purified porcine surfactant served as a further control. Lamellar bodies and lung ultrasound score were also measured in a subset of the neonates treated with CPAP. Surfactant was administered according to the European guidelines, and clinical data were collected prospectively. Surfactant activity was measured as adsorption at the air/liquid interface and given in relative fluorescent units (RFU). Results: Surfactant activity differed among native porcine surfactant (median, 4863 RFU; IQR, 4405-5081 RFU), healthy term neonates (median, 2680 RFU; IQR, 2069-3050 RFU), and preterm neonates with RDS (median, 442 RFU; IQR, 92-920 RFU; P < .0001). The neonates who failed CPAP had lower surfactant activity compared with those who did not fail CPAP (median, 92 RFU; IQR, 0-315 RFU vs 749 RFU; IQR, 360-974 RFU; P = .0002). Differences between groups were more evident beyond 20-30 minutes of fluorescence; the 30-minute time point showed the highest area under the curve (0.84; P < .001) and the best cutoff level (170 RFU; specificity, 72%; sensitivity, 96%) for the prediction of CPAP failure. Surfactant activity at 30 minutes was significantly correlated with lamellar bodies (r = 0.51, P = .006) and lung ultrasound score (r = -0.39, P = .013). Conclusion: This technique has the potential to be developed into a fast, simple-to-interpret clinical test. The SAT can reliably identify preterm infants with subsequent CPAP failure and shows promise as a screening test for surfactant replacement in preterm neonates

Pulmonary hypertension associated with myeloproliferative disorders: a retrospective study of ten cases

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