Allergy news

30.03.2010

Journal: International Archives of Allergy and Immunology

Author: Wang Wei, Yongge Liu, Yonghong Wang, Yuhong Zhao, Jianxin He, Xiang Li, Kunling Shen 

Induction of  CD4+CD25+Foxp3+IL-10+ T Cells in HDM-Allergic Asthmatic Children with or without SIT

Background: Regulatory T cells and immunosuppressive cytokines, such as IL-10 and TGF-β1, may have a role in clinically effective allergen-specific immunotherapy. IL-10-secreting regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. The aim of this study was to evaluate the frequency and function of regulatory T cells in the response to house dust mite (HDM) immunotherapy.

Methods: PBMCs were isolated from 27 HDM-allergic asthmatic children who underwent immunotherapy for 1.5–2 years (SIT group) and from 27 matched treated asthmatic children allergic to HDM (asthma group). After 48 h of in vitro stimulation with HDM extracts, regulatory T cells were measured by flow cytometry. Production of IL-4, IFN-γ and TGF-β1 in supernatants from allergen-stimulated cultures and the PBMC proliferations were measured by ELISA. Sera were tested for allergen-specific IgE using the ImmunoCAP 100 assay.

Results: Patients undergoing immunotherapy produced significantly more IL-10 and showed a significant reduction in proliferation induced by HDM extract compared with the asthma group. In cultures stimulated with HDM extract, the amounts of IL-4 and TGF-β were lower and the amounts of IFN-γ were higher in the SIT group compared with the asthma group.

Conclusion: There is a functional, but quantitative, insufficiency of Treg cells in allergic asthmatic children, which was reversed in SIT-treated children. SIT can up-regulate the function of CD4+CD25+Foxp3+ Treg cells.l

29 Mar. 2010 Journal: The Journal of Immunology

Most allergens exist in several variants (isoallergens), each of which may be recognized differently by patient IgE. We have previously shown that several properties of the IgE repertoire, including IgE affinity and IgE clonality, are important factors determining degranulation responses of effector cells involved in type I allergic reactions. However, less is known about how the repertoire of naturally occurring isoallergens may affect this response. Thus, in this study, we investigated how individual rIgE Ab clones derived from a human subject are able to distinguish among variants of Der p 2 isoallergens and assessed the impact on basophil degranulation. Biacore analyses showed that individual rIgE clones cloned from an individual allergic to house dust mites recognized Der p 2 with binding affinities varying up to 100-fold between different Der p 2 isoforms. In a well-defined biological system consisting of human basophils sensitized with low rIgE clonality, degranulation responses were directly related to rIgE affinity toward particular rDer p 2 isoallergens. However, basophils sensitized with polyclonal patients’ sera showed no differences in degranulation responses toward the different rDer p 2 isoallergens. In conclusion, our study shows that individual IgE Abs are able to bind single allergens with a broad range of affinities due to natural isoallergen variations, contributing further to the overall complexity of IgE–allergen interactions at the effector cell surface, which is, however, blurred by the polyclonal nature of patients’ IgE repertoires.

22 Mar. 2010 Journal: Pediatric Allergy and Immunology

Author: Lynette Pei-Chi Shek, Angeline R. Chong, Shu E. Soh, Nge Cheong, Audrey S. M. Teo, Fong C. Yi, Yoke C. Giam, Kaw Y. Chua and Hugo P. Van Bever

 Specific profiles of house dust mite sensitization in children with asthma and in children with eczema

Sensitization to house dust mites (HDM) is highly prevalent among the young atopic population in Singapore. Previously published data suggest that individuals with skin allergies show preferred sensitization to Dermatophagoides pteronyssinus while individuals with pure respiratory allergies show preferred sensitization to Blomia tropicalis. The aim of our study was to compare the sensitization profiles between children with asthma and those with eczema to D. pteronyssinus and B. tropicalis and their specific allergens. A total of 60 children, 30 with asthma and 30 with eczema were recruited. IgE levels specific for a panel of HDM allergens from the two mite species were measured using enzyme-linked immunosorbent assay. The asthma group showed highest sensitization to Blo t5 while the eczema group showed highest sensitization to Der p5. Comparison between the two disease groups showed that the eczema group had significantly higher IgE levels for Der p (p = 0.042) and its allergens Der p1 (p = 0.019) and Der p5 (p = 0.001). Generally, the eczema group was more sensitized to the panel of allergens compared to the asthma group. Individuals with asthma and those with eczema showed different sensitization profiles to HDM. These findings highlighted possible mechanisms for different manifestation of allergy.

15 Mar. 2010 Journal: The Journal of Allergy and Clinical Immunology

Author: Ariana C. Yang, L. Karla Arruda, Ana Beatriz R. Santos, Michelle C.R. Barbosa, Martin D. Chapman, Clóvis E.S. Galvão, Jorge Kalil, Fábio F. Morato-Castro

 Measurement of IgE antibodies to shrimp tropomyosin is superior to skin prick testing with commercial extract and measurement of IgE to shrimp for predicting clinically relevant allergic reactions after shrimp ingestion

Background: Shrimp is a frequent cause of food allergy. Tropomyosin is the major allergen in shrimp, and it shares homology to tropomyosins from other crustaceans, dust mites, cockroach, and parasites.

Objective: The aim of this study was to determine the value of detection of IgE to shrimp tropomyosin in the diagnosis of shrimp allergy.

Methods: We have studied 35 patients with asthma, rhinitis, or both who were sensitized to Dermatophagoides pteronyssinus. All subjects underwent skin prick testing in addition to double-blind, placebo-controlled food challenges (DBPCFC); oral open challenges; or both with shrimp. Measurements of IgE to shrimp and shrimp tropomyosin were carried out by means of CAP and chimeric ELISA, respectively.

Results: Oral challenges confirmed the diagnosis of shrimp allergy in 7 patients. IgE measurement to shrimp tropomyosin was positive in 71.4% of the patients with shrimp allergy. Of the 28 patients without shrimp allergy, only 7.1% (2/28) had IgE to shrimp tropomyosin compared with 25% (7/28) who had IgE to shrimp and 35.7% (10/28) who had positive skin prick test responses to shrimp. Sensitivity was similar for all 3 methods (71.4%); in contrast, specificity of IgE to shrimp tropomyosin (92.8%) was greater than that of IgE to shrimp (75%) and skin prick testing (64.2%). With regard to diagnostic efficiency, measurement of IgE to shrimp tropomyosin was superior to measurement of IgE to shrimp and skin prick testing (88.5%, 74.2%, and 65.7%, respectively).

Conclusion: Use of measurements of IgE to shrimp tropomyosin provided added value to the diagnosis of shrimp allergy.

15 Mar. 2010 Journal: The Journal of Allergy and Clinical Immunology

Author: Geoffrey A. Mueller, Lori L. Edwards, Jim J. Aloor, Michael B. Fessler, Jill Glesner, Anna Pomés, Martin D. Chapman, Robert E. London, Lars C. Pedersen

 The structure of the dust mite allergen Der p 7 reveals similarities to innate immune proteins

Background: Sensitization to house dust mite allergens is strongly correlated with asthma. Der p 7 elicits strong IgE antibody and T-cell responses in patients with mite allergy. However, the structure and biological function of this important allergen are unknown. Allergen function might contribute to allergenicity, as shown for the protease activity of group 1 mite allergens and the interaction with the innate immune system by group 2 mite allergens.

Objective: We sought to determine the crystal structure of Der p 7 and to investigate its biological function.

Methods: X-ray crystallography was used to determine the Der p 7 structure. Nuclear magnetic resonance analysis and biochemical assays were used to examine the binding of Der p 7 to predicted ligands.

Results: Der p 7 has an elongated structure, with two 4-stranded antiparallel β-sheets that wrap around a long C-terminal helix. The fold of Der p 7 is similar to that of LPS-binding protein (LBP), which interacts with Toll-like receptors after binding LPS and other bacterially derived lipid ligands. Nuclear magnetic resonance and biochemical assays indicate that Der p 7 does not bind LPS but binds with weak affinity to the bacterial lipopeptide polymyxin B in the predicted binding site of Der p 7.

Conclusions: Der p 7 binds a bacterially derived lipid product, a common feature of some allergens. The finding that the group 7, as well as the group 2, mite allergens are structurally similar to different proteins in the Toll-like receptor pathway further strengthens the connections between dust mites, innate immunity, and allergy.

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