Nitration of the Egg-Allergen Ovalbumin Enhances Protein Allergenicity but Reduces the Risk for Oral Sensitization in a Murine Model of Food Allergy

Nitration of proteins on tyrosine residues, which can occur due to polluted air under "summer smog" conditions, has been shown to increase the allergic potential of allergens. Since nitration of tyrosine residues is also observed during inflammatory responses, this modification could directly influence protein immunogenicity and might therefore contribute to food allergy induction. In the current study we have analyzed the impact of protein nitration on sensitization via the oral route.BALB/c mice were immunized intragastrically by feeding untreated ovalbumin (OVA), sham-nitrated ovalbumin (snOVA) or nitrated ovalbumin (nOVA) with or without concomitant acid-suppression. To analyze the impact of the sensitization route, the allergens were also injected intraperitoneally. Animals being fed OVA or snOVA under acid-suppressive medication developed significantly elevated levels of IgE, and increased titers of specific IgG1 and IgG2a antibodies. Interestingly, oral immunizations of nOVA under anti-acid treatment did not result in IgG and IgE formation. In contrast, intraperitoneal immunization induced high levels of OVA specific IgE, which were significantly increased in the group that received nOVA by injection. Furthermore, nOVA triggered significantly enhanced mediator release from RBL cells passively sensitized with sera from allergic mice. Gastric digestion experiments demonstrated protein nitration to interfere with protein stability as nOVA was easily degraded, whereas OVA and snOVA remained stable up to 120 min. Additionally, HPLC-chip-MS/MS analysis showed that one tyrosine residue (Y(107)) being very efficiently nitrated is part of an ovalbumin epitope recognized exclusively after oral sensitization.These data indicated that despite the enhanced triggering capacity in existing allergy, nitration of OVA may be associated with a reduced de novo sensitizing capability via the oral route due to enhanced protein digestibility and/or changes in antibody epitopes

Risk of infection in the first year of life in preterm children: An Austrian observational study.

Newborns, especially preterm infants, have an immature immune system, which, in combination with the required medical interventions necessary for keeping the neonate alive may lead to an increased risk of infection. Even after reaching stability and adapting to the environment, preterm infants have adverse prognoses regarding infections and long-term outcomes compared to their full-term counterparts. The objective of this study was to research differences in the number and severity of infections between preterm and full-term infants during their first year of life. To answer this question, a monocentric prospective study was conducted in a pediatric practice in Vienna, including 71 full-term infants and 72 preterm infants who were observed during their first year of life regarding occurring infections. In respective samples, there was a significantly higher total number of infections in preterm (mean 6.01 ± 3.90) compared to full-term infants (3.85 ± 1.72) during the observation period of one year. Particularly the count of respiratory and severe infections was considerably higher in preterm infants. Otorhinolaryngeal infections were the most frequent of all types of infections in both groups. The pregnancy period, number of siblings, and length of the postnatal hospital stay, were observed as significantly influencing factors which affected the total number of infections. The group of early term infants (37+0 weeks to 38+6) was not significantly different to late term babies (>39+0). The acquired knowledge about the increased risk of infections should lead to a more extensive care for preterm infants, with the objective of reducing the rates of complications, morbidity and mortality in this vulnerable age group in the future

Respiratory Infections in Children During a Covid-19 Pandemic Winter

BACKGROUND: The Covid-19 pandemic compelled the implementation of measures to curb the SARS CoV-2 spread, such as social distancing, wearing FFP2 masks, and frequent hand hygiene. One anticipated ramification of these measures was the containment of other pathogens. This prospective, longitudinal study aimed to investigate the spread of 22 common seasonal non-SARS-CoV-2 pathogens, such as RSV and influenza, among children with an acute respiratory infection during a pandemic. METHODS: Three hundred ninety children (0-24 months) admitted to Vienna's largest pediatric center with acute respiratory infection (November 2020-April 2021) were included in this study. The researchers tested nasal swabs for 22 respiratory pathogens by Multiplex PCR, documented clinical features and treatment, and evaluated data for a potential connection with the lockdown measures then in force. RESULTS: The 448 smears revealed the most common pathogens to be rhino-/enterovirus (41.4%), adenovirus (2.2%), and coronavirus NL63 (13.6%). While the first two were active throughout the entire season, coronaviruses peaked in the first trimester of 2021 in conjunction with the lift of the lockdown period (OR 4.371, 95%CI 2.34-8.136, P < 0.001). RSV, metapneumovirus, and influenza were absent. CONCLUSION: This prospective, longitudinal study shows that Covid-19 measures suppressed the seasonal activity of influenza, RSV, and metapneumovirus among very young children, but not of rhino-/enterovirus and adenovirus. The 0-24 month-olds are considered the lowest risk group and were only indirectly affected by the public health measures. Lockdowns were negatively associated with coronaviruses infections

Plasma Levels of the Bioactive Sphingolipid Metabolite S1P in Adult Cystic Fibrosis Patients: Potential Target for Immunonutrition?

Recent research has linked sphingolipid (SL) metabolism with cystic fibrosis transmembrane conductance regulator (CFTR) activity, affecting bioactive lipid mediator sphingosine-1-phosphate (S1P). We hypothesize that loss of CFTR function in cystic fibrosis (CF) patients influenced plasma S1P levels. Total and unbound plasma S1P levels were measured in 20 lung-transplanted adult CF patients and 20 healthy controls by mass spectrometry and enzyme-linked immunosorbent assay (ELISA). S1P levels were correlated with CFTR genotype, routine laboratory parameters, lung function and pathogen colonization, and clinical symptoms. Compared to controls, CF patients showed lower unbound plasma S1P, whereas total S1P levels did not differ. A positive correlation of total and unbound S1P levels was found in healthy controls, but not in CF patients. Higher unbound S1P levels were measured in ΔF508-homozygous compared to ΔF508-heterozygous CF patients (p = 0.038), accompanied by higher levels of HDL in ΔF508-heterozygous patients. Gastrointestinal symptoms were more common in ΔF508 heterozygotes compared to ΔF508 homozygotes. This is the first clinical study linking plasma S1P levels with CFTR function and clinical presentation in adult CF patients. Given the emerging role of immunonutrition in CF, our study might pave the way for using S1P as a novel biomarker and nutritional target in CF

Characterization of Vibrio cholerae neuraminidase as an immunomodulator for novel formulation of oral allergy immunotherapy

To improve current mucosal allergen immunotherapy Vibrio cholerae neuraminidase (NA) was evaluated as a novel epithelial targeting molecule for functionalization of allergen-loaded, poly(D,L-lactide-co-glycolide) (PLGA) microparticles (MPs) and compared to the previously described epithelial targeting lectins wheat germ agglutinin (WGA) and Aleuria aurantia lectin (AAL). All targeters revealed binding to Caco-2 cells, but only NA had high binding specificity to -L fucose and monosialoganglioside-1. An increased transepithelial uptake was found for NA-MPs in a M-cell co-culture model. NA and NA-MPs induced high levels of IFN- and IL10 in naive mouse splenocytes and CCL20 expression in Caco-2. Repeated oral gavage of NA-MPs resulted in a modulated, allergen-specific immune response. In conclusion, NA has enhanced M-cell specificity compared to the other targeters. NA functionalized MPs induce a Th1 and T-regulatory driven immune response and avoid allergy effector cell activation. Therefore, it is a promising novel, orally applied formula for allergy therapy.(VLID)469022

Supplementarytables_The surge of RSV and other respiratory viruses among children during the second COVID-19 pandemic winter season.docx

BackgroundThe non-pharmaceutical measures in the first Covid-19 winter season significantly impacted respiratory pathogens such as RSV, influenza, or metapneumovirus, which cause respiratory infections, especially in infants and young children. This longitudinal prospective study aimed to determine how less strict measures affect the pathogen profile in the second winter season.MethodsFrom September 2021 till the end of March 2022, 678 children (0–36 months) admitted to Vienna's largest pediatric center with an acute respiratory infection were enrolled in this study. The researchers performed nasal swabs and tested them by multiplex PCR for 23 respiratory pathogens, chronicled clinical features and treatment, and analyzed the effect of lockdown on the pathogen prevalence.ResultsThe 815 smears of 678 children revealed the most common pathogens to be rhino-/enterovirus (38.5%), RSV (26.7%), and metapneumovirus (7.2%). The lockdown interrupted the early RSV onset in September [RR 0.367, CI (0.184–0.767), p = 0.003], while no effects on the other pathogens were found. Metapneumovirus started circulating in January. Influenza was only sporadically detected. The hospitalization rate was significantly higher than last season due to RSV [OR 4.089, 95%CI (1.414–11.827), p-adj = 0.05].ConclusionWith more flexible non-pharmaceutical measures, children aged 0–36 months started presenting again with viral pathogens, such as RSV and metapneumovirus. RSV, associated with a high hospitalization rate, had a very early onset with an abrupt interruption due to the only lockdown.</p