Journal of allergy最新文献

Background & Objective. Ultrarush induction for specific venom immunotherapy has been shown to be reliable and efficacious in adults. In this study its safety and tolerance in children was evaluated. Methods. Retrospective analysis of 102 ultrarush desensitizations carried out between 1997 and 2005 in 94 children, aged 4 to 15 years. Diagnosis and selection for immunotherapy were according to recommendations of the European Academy of Allergy and Clinical Immunology. Systemic adverse reactions (SARs) were described using the classification of H. L. Mueller. Results. All patients reached the cumulative dose of 111.1 μg hymenoptera venom within 210 minutes. Six patients (6%) had allergic reactions grade I; 2 patients (2%) grade II and 5 patients (5%) grade III. Three patients (3%) showed unclassified reactions. SARs did not occur in the 15 patients aged 4 to 8 years and they were significantly more frequent in girls (29%) compared with boys (12%) (P = 0.034, multivariant analysis) and in bee venom extract treated patients (20%) compared to those treated with wasp venom extract (8%) (OR 0.33, 95% Cl 0.07-1.25). Conclusion. Initiation of specific immunotherapy by ultrarush regimen is safe and well tolerated in children and should be considered for treating children with allergy to hymenoptera venom.

Intestinal epithelial barrier plays a critical role in the maintenance of gut homeostasis by limiting the penetration of luminal bacteria and dietary allergens, yet allowing antigen sampling for the generation of tolerance. Undigested proteins normally do not gain access to the lamina propria due to physical exclusion by tight junctions at the cell-cell contact sites and intracellular degradation by lysosomal enzymes in enterocytes. An intriguing question then arises: how do macromolecular food antigens cross the epithelial barrier? This review discusses the epithelial barrier dysfunction in sensitized intestine with special emphasis on the molecular mechanism of the enhanced transcytotic rates of allergens. The sensitization phase of allergy is characterized by antigen-induced cross-linking of IgE bound to high affinity FcεRI on mast cell surface, leading to anaphylactic responses. Recent studies have demonstrated that prior to mast cell activation, food allergens are transported in large quantity across the epithelium and are protected from lysosomal degradation by binding to cell surface IgE and low-affinity receptor CD23/FcεRII. Improved immunotherapies are currently under study including anti-IgE and anti-CD23 antibodies for the management of atopic disorders.

Sublingual immunotherapy (SLIT) has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type I allergy of nasal mucosa. Nevertheless, its mechanisms need to be further investigated. In this study, we constructed an effective murine model of sublingual immunotherapy in allergic rhinitis, in which mice were sublingually administered with ovalbumin (OVA) followed by intraperitoneal sensitization and nasal challenge of OVA. Sublingually treated mice showed significantly decreased specific IgE responses as well as suppressed Th2 immune responses. Sublingual administration of OVA did not alter the frequency of CD4(+)CD25(+) regulatory T cells (Tregs), but led to upregulation of Foxp3- and IL-10-specific mRNAs in the Tregs of cervical lymph nodes (CLN), which strongly suppressed Th2 cytokine production from CD4(+)CD25(-) effector T cells in vitro. Furthermore, sublingual administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser DNA together with OVA suppressed allergic responses. These results suggest that IL-10-expressing CD4(+)CD25(+)Foxp3(+) Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice that received SLIT.

Many common foods including cow's milk, hen's egg, soya, peanut, tree nuts, fish, shellfish, and wheat may cause food allergies. The prevalence of these immune-mediated adverse reactions to foods ranges from 0.5% to 9% in different populations. In simple terms, the cornerstone of managing food allergy is to avoid consumption of foods causing symptoms and to replace them with nutritionally equivalent foods. If poorly managed, food allergy impairs quality of life more than necessary, affects normal growth in children, and causes an additional economic burden to society. Delay in diagnosis may be a further incremental factor. Thus, an increased awareness of the appropriate procedures for both diagnosis and management is of importance. This paper sets out to present principles for taking an allergy-focused diet history as part of the diagnostic work-up of food allergy. A short overview of guidelines and principles for dietary management of food allergy is discussed focusing on the nutritional management of food allergies and the particular role of the dietitian in this process.

Bronchial asthma is a chronic disorder accompanied by phenotypic transitions of bronchial epithelial cells, smooth muscle cells, and fibroblasts. Human bronchial fibroblasts (HBFs) derived from patients with diagnosed asthma display predestination towards TGF-β-induced phenotypic switches. Since the interference between TGF-β and GSK-3β signaling contributes to pathophysiology of chronic lung diseases, we investigated the effect of lithium, a nonspecific GSK-3β inhibitor, on TGF-β(1)-induced fibroblast to myofibroblast transition (FMT) in HBF and found that the inhibition of GSK-3β attenuates TGF-β(1)-induced FMT in HBF populations derived from asthmatic but not healthy donors. Cytoplasmically sequestrated β-catenin, abundant in TGF-β(1)/LiCl-stimulated asthmatic HBFs, most likely interacts with and inhibits the nuclear accumulation and signal transduction of Smad proteins. These data indicate that the specific cellular context determines FMT-related responses of HBFs to factors interfering with the TGF-β signaling pathway. They may also provide a mechanistic explanation for epidemiological data revealing coincidental remission of asthmatic syndromes and their recurrence upon the discontinuation of lithium therapy in certain psychiatric diseases.

Airflow within the airways is determined directly by the lumenal area of that airway. In this paper, we consider several factors which can reduce airway lumenal area, including thickening and/or active constriction of the airway smooth muscle (ASM). The latter cell type can also contribute in part to inflammation, another feature of asthma, through its ability to take on a synthetic/secretory phenotype. The ASM therefore becomes a strategically important target in the treatment of asthma, given these key contributions to the pathophysiology of that disease. Pharmacological approaches have been developed to elicit relaxation of the ASM, but these are not always effective in all patients, nor do they address the long-term structural changes which impinge on the airway lumen. The recent discovery that thermal energy can be used to ablate smooth muscle has led to the development of a novel physical intervention-bronchial thermoplasty-in the treatment of asthma. Here, we review the evolution of this novel approach, consider some of the possible mechanisms that account for its salutary effects, and pose new questions which may lead to even better therapies for asthma.

The study of immune regulation and tolerance has been traditionally associated with self/nonself-discrimination. However, the finding that dominant tolerance, a model that puts in evidence the active role of regulatory T cells, can develop to nonself-antigens suggests that the imposition of tolerance can be context dependent. This paper reviews the emerging field of acquired immune tolerance to non-self antigens, with an emphasis on the different subsets of induced regulatory T cells that appear to specialize in specific functional niches. Such regulatory mechanisms are important in preventing the onset of allergic diseases in healthy individuals. In addition, it may be possible to take advantage of these immune regulatory mechanisms for the induction of tolerance in cases where pathological immune responses are generated to allergens occurring in nature, but also to other immunogens such as biological drugs developed for medical therapies.

Asthma is a complex disease regulated by the interplay of a large number of underlying mechanisms which contribute to the overall pathology. Despite various breakthroughs identifying genes related to asthma, our understanding of the importance of the genetic background remains limited. Although current therapies for asthma are relatively effective, subpopulations of asthmatics do not respond to these regimens. By unlocking the role of these underlying mechanisms, a source of novel and more effective treatments may be identified. In the new age of high-throughput technologies, gene-expression microarrays provide a quick and effective method of identifying novel genes and pathways, which would be impossible to discover using an individual gene screening approach. In this review we follow the history of expression microarray technologies and describe their contributions to advancing our current knowledge and understanding of asthma pathology.

Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G(1) cell cycle progression-cyclin D1-in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

Parents often overreport adherence to asthma treatment regimens making accurate assessment of medication adherence in clinical practice difficult. This study was conducted to compare two adherence assessment methods clinicians may choose from when assessing patient inhaled corticosteroid (ICS) adherence: parental report and dose counter measurements of metered-dose inhaler (MDI) actuation. Participants included children (N = 50) with persistent asthma and their parents (N = 50). At enrollment, children received a new, marked ICS at the dose prescribed by their physician. Thirty days following enrollment, we measured ICS adherence by parental report and objectively, with a dose counter. Parental report overestimated ICS adherence when compared to dose counter. We found a statistically significant overall difference between parental report and objectively measured adherence. A dose counter that most ICS inhalers are equipped with may be a more reliable alternative measure of ICS adherence in a clinical practice setting.