Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge.

BACKGROUND: An emerging paradigm holds that resistance to the development of allergic diseases, including allergic rhinoconjunctivitis, relates to an intact epithelial/epidermal barrier during early childhood. Conceivably, the immunologic and genomic footprint of this resistance is preserved in nonatopic, nonallergic adults and is unmasked during exposure to an aeroallergen. OBJECTIVE: The aim of this study was to obtain direct support of the epithelial/epidermal barrier model for allergic rhinoconjunctivitis. METHODS: Twenty-three adults allergic to house dust mites (HDMs) (M+) and 15 nonsensitive, nonallergic (M-) participants completed 3-hour exposures to aerosolized HDM (Dermatophagoides pteronyssinus) powder on 4 consecutive days in an allergen challenge chamber. We analyzed: (1) peripheral blood leukocyte levels and immune responses; and (2) RNA sequencing-derived expression profiles of nasal cells, before and after HDM exposure. RESULTS: On HDM challenge: (1) only M+ persons developed allergic rhinoconjunctivitis symptoms; and (2) peripheral blood leukocyte levels/responses and gene expression patterns in nasal cells were largely concordant between M+ and M- participants; gross differences in these parameters were not observed at baseline (pre-exposure). Two key differences were observed. First, peripheral blood CD4+ and CD8+ T-cell activation levels initially decreased in M- participants versus increased in M+ participants. Second, in M- compared with M+ participants, genes that promoted epidermal/epithelial barrier function (eg, filament-aggregating protein [filaggrin]) versus inflammation (eg, chemokines) and innate immunity (interferon) were upregulated versus muted, respectively. CONCLUSION: An imprint of resistance to HDM challenge in nonatopic, nonallergic adults was muted T-cell activation in the peripheral blood and inflammatory response in the nasal compartment, coupled with upregulation of genes that promote epidermal/epithelial cell barrier function.

Allergen stabilities and compatibilities in mixtures of high-protease fungal and insect extracts.

BACKGROUND: Current practice guidelines state that protease-rich fungal and insect extracts can be combined when preparing immunotherapy vaccines, but data supporting the stability of allergens in these mixtures have not been reported. OBJECTIVE: To determine the stabilities and compatibilities of Alternaria alternata and German cockroach allergens in mixtures with other high-protease fungal and insect (cockroach, imported fire ant) extracts at final extract concentrations consistent with injection dose targets for maintenance immunotherapy. METHODS: Mixtures containing Alternaria, German cockroach, and other fungal and insect extracts frequently included in immunotherapy vaccines were analyzed by a combination of quantitative analyses (enzyme-linked immunosorbent assays for multiallergen immunoglobulin E [IgE]-binding potency, major Alternaria allergen Alt a 1, and major German cockroach allergens Bla g 1 and Bla g 2) and qualitative methods (immunoblotting). Mixtures and analogous single-extract controls containing 10 to 50% glycerin were evaluated after storage for up to 12 months at 2°C to 8°C. RESULTS: Mixtures of extracts within the same phylogenetic groups (fungal-fungal, insect-insect) retained favorable Alternaria and German cockroach allergen levels and activities under most conditions examined. For several cross-taxonomic (fungal-insect) extract combinations at 10 to 25% glycerin concentrations, different immunochemical test methods measuring single (major) or multiple allergens yielded threefold to 10-fold variations in allergen recoveries. CONCLUSION: Allergen compatibilities can be compromised in some fungal-insect extract mixtures, contrary to current immunotherapy practice parameter recommendations. Separation of these products into different treatment vials may be required to produce stable mixtures for subcutaneous immunotherapy. Data from assay methodologies with distinct binding specificities provide a critical assessment of allergen activities in high-protease extract mixtures.

Sublingual immunotherapy.

PURPOSE OF REVIEW: Sublingual immunotherapy is an established treatment option for allergic rhinitis in many European countries, but it is not approved in the United States and is considered investigational. Sublingual immunotherapy has received increasing attention in the United States as an alternative to subcutaneous immunotherapy for the treatment of allergic rhinitis and possibly asthma. RECENT FINDINGS: Evidence for the safety and efficacy of sublingual immunotherapy is accumulating. The immunological effects of sublingual immunotherapy appear to be similar to those of subcutaneous immunotherapy, but their mechanisms may differ. The unique attributes of sublingual immunotherapy may offer advantages in selected patients. Controlled studies are being extended to evaluate sublingual immunotherapy for other indications, including allergic asthma, latex allergy, atopic dermatitis and food allergies. SUMMARY: Increasing data support the safety and efficacy of sublingual immunotherapy and its validity as a first-line treatment option for allergic rhinitis; however, acceptance in the United States is hindered by the lack of confirmatory evidence with United States-licensed products and the reluctance of allergists to accept evidence based on European studies and products. The future of sublingual immunotherapy in the United States will require addressing regulatory, economic and medical criteria.

Stability of standardized grass, dust mite, cat, and short ragweed allergens after mixing with mold or cockroach extracts.

BACKGROUND: Limited data are available on the immunochemical compatibilities of standardized and nonstandardized allergen extracts in immunotherapy vaccines. Extract combinations recommended in immunotherapy practice parameters are based primarily on theoretical considerations rather than on actual product compatibilities. OBJECTIVES: To determine the stabilities of standardized grass, short ragweed, dust mite, and cat extracts after mixing with fungal and cockroach extracts at final product concentrations similar to those recommended for maintenance immunotherapy injections. METHODS: Mixtures were prepared using individual products from multiple sources at variable glycerin concentrations and were analyzed after storage for up to 1 year at 2 degrees C to 8 degrees C. Quantitative analyses included radial immunodiffusion assays for cat Fel d 1 and short ragweed Amb a 1 and human IgE enzyme-linked immunosorbent assay inhibitions for meadow fescue grass and dust mite allergens. Immunoblot analyses provided qualitative patterns of IgE binding. RESULTS: Meadow fescue grass allergens were unstable after mixing with fungal or cockroach extracts but were highly compatible with dust mite extracts from numerous commercial sources. Fescue and dust mite allergen recoveries varied considerably when mixed with different mold extracts. The presence of cockroach extracts reduced dust mite allergen potencies but retained moderate levels of cat and short ragweed allergen activities. In all cases examined, glycerin provided concentration-dependent improvements in allergen recoveries. CONCLUSIONS: Several allergen extract combinations generally regarded as unstable by current practice parameters seem to possess considerable biochemical compatibilities. Use of these mixtures in immunotherapy vaccines is supported for practitioners seeking to optimize formulations, doses, and treatment regimens for their patients.

Características imunológicas da sensibilizaçäo acarina respiratória no Rio de Janeiro / Immunological characterization of the respiratory mite sensitization in Rio de Janeiro

Os dados imunológicos da sensibilizaçao acarina respiratória no Rio de Janeiro foram obtidos através da correlaçao entre os resultados de testes alérgicos cutâneos, RAST séricos, análises qualitativa e quatitativa microscópicas acarinas de amostras de poeira domiciliar e a determinaçao simultânea da concentraçao de antígenos Der p I Der f I. Os resultados demonstram a importância dos ácaros Dermatophagoides petronyssinus e Blomia tropicalis na patogênese da asma e/ou rinite alérgicas em nosso meio.

Sensibilizaçäo acarina na atopia respiratória do Rio de Janeiro: consideraçöes preliminares / Sensitization in respiratory atopy of the Rio de Janeiro: preliminary considerations

Avaliamos 540 pacientes com asma e/ou rinite no Rio de Janeiro. Todos foram estudados com testes alérgicos cutâneos (multi-Test, USA). Foram empregados os seguintes antígenos: poeira domiciliar americana (Hd), poeira domiciliar brasileira (Bhd), Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dp), Blomia tropicalis (Bt), Chortoglyphus arcuatus (Ca), Lepidoglyphus destructor (Ld) e aleuroglyphus ovatus (Ao). A atopia respiratória no Rio de Janeiro é representada com maior freqüência pela associaçäo da asma com a rinite. Cerca de 65 por cento, dos pacientes observados apresentaram testes alérgicos cutâneos positivos. Os principais ácaros indutores da sensibilizaçäo alérgica foram Dp e Bt. Concluímos, também, que os testes com Bt säo mais sensíveis do que os com Dp. Há reaçöes cruzadas antigênicas entre todos os extratos alegênicos utilizados