The efficacy and safety of preventive allergen immunotherapy (pAIT) in children are currently under investigation. Here, we provide an overview of pAIT with respiratory allergens concerning the ...prevention of new sensitizations, allergic disease onset and progression as well as further immunomodulatory effects. Three databases were searched for clinical pAIT studies in children. Selected publications were reviewed for preventive outcomes according to prevention level (primary, secondary, and tertiary), allergen type, administration route, dose, and treatment duration. The primary prevention approach appears safe but showed no allergen‐specific effect on new sensitizations. Secondary prevention seems feasible and may induce regulatory T cell‐mediated immunotolerance. The number of studies at these prevention levels is limited. Tertiary prevention with grass and/or tree pollen‐based pAIT has shown efficacy in preventing disease progression from allergic rhinitis/conjunctivitis to asthma. Data on tertiary pAIT with house dust mites and other allergen types are inconclusive. Subcutaneous and sublingual routes appear similarly effective, but head‐to‐head comparative paediatric studies are scarce. Additionally, there are fewer placebo‐controlled studies. Nevertheless, immunomodulatory outcomes of pAIT are encouraging. Currently, limited but favourably suggestive evidence is available for preventing respiratory allergic diseases in children by pAIT. Primary and secondary prevention have potential and warrant further investigation through well‐designed studies.
Background
The oligosaccharide galactose‐α‐1,3‐galactose (α‐Gal), present in mammalian proteins and lipids, causes an unusual delayed allergic reaction 3 to 6 hours after ingestion of mammalian meat ...in individuals with IgE antibodies against α‐Gal. To better understand the delayed onset of allergic symptoms and investigate whether protein‐bound or lipid‐bound α‐Gal causes these symptoms, we analyzed the capacity of α‐Gal conjugated proteins and lipids to cross a monolayer of intestinal cells.
Methods
Extracts of proteins and lipids from beef were prepared, subjected to in vitro digestions, and added to Caco‐2 cells grown on permeable supports. The presence of α‐Gal in the basolateral medium was investigated by immunoblotting, thin‐layer chromatography with immunostaining and ELISA, and its allergenic activity was analyzed in a basophil activation test.
Results
After addition of beef proteins to the apical side of Caco‐2 cells, α‐Gal containing peptides were not detected in the basolateral medium. Those peptides that crossed the Caco‐2 monolayer did not activate basophils from an α‐Gal allergic patient. Instead, when Caco‐2 cells were incubated with lipids extracted from beef, α‐Gal was detected in the basolateral medium. Furthermore, these α‐Gal lipids were able to activate the basophils of an α‐Gal allergic patient in a dose‐dependent manner.
Conclusion
Only α‐Gal bound to lipids, but not to proteins, is able to cross the intestinal monolayer and trigger an allergic reaction. This suggests that the slower digestion and absorption of lipids might be responsible for the unusual delayed allergic reactions in α‐Gal allergic patients and identifies glycolipids as potential allergenic molecules.
α‐Gal is present in both lipids and proteins from beef, but only when it is bound to beef lipids, the oligosaccharide can cross the Caco‐2 cell monolayer. α‐Gal carried by lipids is packaged by the enterocytes into chylomicrons, which are then able to activate the basophils of an α‐Gal allergic patient. The slower in vivo digestion and absorption of lipids explain the delayed allergic reactions to α‐Gal. α‐Gal: galactose‐ α‐1,3‐galactose
Summary
This statement was written by a group of pulmonologists and pediatric pulmonologists belonging to the corresponding professional associations ÖGP (Austrian Society for Pulmonology) and ÖGKJ ...(Austrian Society for pediatric and adolescent medicine) to provide a concise overview of the latest updates in the 2015 GINA Guidelines and to include aspects that are specific to Austria.
Background Ara h 1, a vicilin; Ara h 2, a 2S albumin; and Ara h 3, a legumin, are major peanut allergens. Ara h 2 is an important predictor of clinical reactivity to peanut, but cosensitization to ...all 3 allergens is correlated with the severity of patients’ symptoms. Objective We investigated whether cosensitization to these 3 allergens is caused by IgE cross-reactivity, despite the fact that they do not display obvious structural or sequence similarities. Methods IgE cross-inhibitions were performed with purified Ara h 1, Ara h 2, and Ara h 3 and IgG-depleted sera from 10 patients with peanut allergy. After an in silico search for similar peptides, IgE ELISA inhibition assays with synthetic peptides were performed. Results Ara h 2 inhibited IgE binding to Ara h 1 (average, 86% ± 13%) and Ara h 3 (average, 96% ± 6%). IgE binding to Ara h 2 was inhibited by Ara h 1 by 78% ± 15% and by Ara h 3 by 80% ± 6%. A subsequent sequence comparison showed that these nonhomologous allergens contained several similar surface-exposed peptides. IgE binding to Ara h 2–derived peptides was completely inhibited by Ara h 1 and Ara h 3. A mixture of these peptides reduced IgE binding to Ara h 1 and Ara h 3 by 20% to 60% and to Ara h 2 by 49% to 89%. Conclusion Occurrence of similar sequences in the 3 major peanut allergens accounts for the high extent of cross-reactivity among them.
The influence of retransplantation on survival for pediatric lung transplant recipients Waseda, Ryuichi; Benazzo, Alberto; Hoetzenecker, Konrad ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
November 2018, 2018-Nov, 2018-11-00, 20181101, Letnik:
156, Številka:
5
Journal Article
Recenzirano
Odprti dostop
We reviewed our 25-year experience in pediatric lung transplantation with the aim to identify trends and influencing factors over time.
We reviewed our prospectively maintained database and analyzed ...all patients younger than age 18 years who underwent primary lung transplantation at Medical University of Vienna between 1990 and 2015.
Eighty-six consecutive patients were enrolled with a mean age of 12.9 ± 4.1 years at primary transplantation. The most frequent indication for primary transplantation was cystic fibrosis (64.0). Bilateral double-lung transplantation was performed in 84 patients (97.7%), including lobar transplantation in 35 patients (40.7%). sixty-eight patients (79.1%) underwent transplant on venoarterial extracorporeal membrane oxygenation and 7 patients (8.1%) utilized cardiopulmonary bypass. The 30-day and in-hospital mortality was 8.1% and 17.4%, respectively, and 1-, 5-, and 10-year overall survival (OS) was 79.0%, 67.5%, and 57.1%, respectively. A significant improvement of OS was observed during the second treatment period after 2003 with a 1-, 5-, and 10-year OS of 86.0%, 73.9%, and 73.9%, respectively (P < .01). Seventeen retransplantations were performed in 14 patients. Twelve patients (85.7%) underwent 15 late elective retransplantations for chronic lung allograft dysfunction resulting in a 1- and 5-year OS of 91.7% and 80.2%, respectively. In contrast, 2 patients (14.3%) who underwent acute retransplantation for primary graft failure died during the postoperative period.
Our outcomes for pediatric lung transplantation have improved over the past 25 years and have become comparable to those for adult transplantation. Elective re-transplantations for pediatric patients were performed successfully, and strongly influenced improved long-term OS.
To the Editor: Peanut allergy is considered a major health problem due to its prevalence, persistence, and association with severe symptoms.1 Previous studies suggest that clinical reactivity to ...allergens might be related to allergen-specific IgE epitope patterns, diversity, and avidity, all of which likely play a role in the effect of IgE on basophils and mast cells.2,3 Previous peptide microarray-based studies have demonstrated a pronounced heterogeneity in the epitope-binding patterns between individual allergic patients apart from a few immunodominant epitopes.2,4-7 Furthermore, elevated IgG4 levels have been associated with protective effects.8 Here, high-density peptide arrays were applied to map linear IgE and IgG4 epitopes at the single amino acid level. Sera from peanut-allergic patients (P1-P6) had extensive IgE and IgG4 reactivity against peanut allergens compared with sera from control subjects (see Fig E1 in this article's Online Repository at www.jacionline.org).
Drug desensitization can be achieved successfully by gradual drug dose increases in different protocols. Most protocols are designed to obtain temporal tolerance. The data on long-term maintenance of ...drug tolerance is scarce. Based on an IgE-mediated colomycin allergy we describe the maintenance of drug tolerance to nebulized drug for the period of 10 years in a 15-year-old cystic fibrosis patient, proceeded by successful rush intravenous desensitization protocol. The mechanism of drug tolerance is largely speculative; however, long-term maintenance of it seems achievable by continuous local drug application.
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