Atopy is a common immune disorder characterized by raised IgE levels, which lead to clinical disorders (i.e. primarily bronchial asthma, atopic dermatitis and allergic rhinoconjuctivitis). Interleukin (IL)-4 and IL-13, derived from T-helper cell type 2 (Th2) subsets, are central in mediating IgE production and development of immediate hypersensitivity. Atopy is also characterized by Th1/Th2 skewing that derives from genetic and environmental factors. The prevalence of atopy has increased in recent decades, especially in developed countries among children and young adults. In the present review, we first discuss the relationship between the Th1/Th2 imbalance and the recent rise of allergy. Second, we present evidence that human genetic variation is also a key factor responsible for atopy.

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Allergen-specific immunotherapy (SIT) involves the administration of gradually increasing amounts of an allergen extract to reduce clinical symptoms of allergy. Well-controlled clinical trials have demonstrated the efficacy of SIT in the treatment of allergic diseases, including rhinoconjunctivitis and asthma, and best practice protocols have been established. Nevertheless, application of this potentially curative treatment is restricted, largely due to the risk of serious adverse events, especially in asthmatics. Although efficacy is high for venom-induced allergy, success rates for the more common aeroallergen-induced disease range from 60 to 80% depending on the allergen. The practice of SIT is currently being refined following major advances in our knowledge of basic immune mechanisms. In particular, new T cell-targeted strategies are being explored with the awareness of the pivotal role allergen-specific T cells play in initiating and regulating the immune response to allergens. Current SIT induces decreased IgE class switching and eosinophil activation by downregulating production of the T helper (Th) 2-type cytokines interleukin (IL)-4 and IL-5. Therefore, allergen preparations that have ablated IgE binding while retaining T cell reactivity should still be clinically effective but have substantially improved safety. These approaches include the use of small peptides based on dominant T cell epitopes of allergens and chemically modified or recombinant allergen molecules. Both approaches have already been tested, with promising results, in animal models; peptide immunotherapy has been shown effective in clinical trials. Defined hypoallergenic molecules or peptides offer ease of standardization in addition to efficacy and safety and will result in more widespread use of SIT in clinical practice. Elucidation of mechanisms for downregulating Th2-predominant responses to allergen by SIT will enable the development of laboratory assays for monitoring clinical efficacy.

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Background: The diagnosis of allergic diseases with recombinant allergens allows us to detect antibodies specific for single allergens in extracts. The aim of the present study was to assess the early effect of grass pollen immunotherapy on IgE and IgG4 responses to eight purified grass pollen allergens in patients undergoing hyposensitization treatment.
Methods: The sera of 22 consecutive atopic individuals undergoing cluster regimen grass pollen immunotherapy were analyzed for IgE and IgG4 antibodies specific for grass pollen allergens (Phl p 1, 2, 4, 5, 6, 7, 11, 12). Two serum samples were taken, one before the start of therapy and one between 12 and 15 weeks after the first immunization. Immunotherapy was performed with two allergy vaccines comprising a standardized extract aluminum-adsorbed grass pollen mix and a standardized extract of grass pollen mix adsorbed onto calcium phosphate.
Results: One treated patient showed a specific IgE conversion from negative (< 0.35 kUA/L) to positive in the capsulated hydrophilic carrier polymer (CAP) test for Phl p 2, 1 and 4 (1.89, 0.84 and 0.68 kUA/L, respectively). The sera of 10 of 11 patients treated with alluminum-adsorbed grass pollen extract showed a significant increase in specific IgG4 towards natural Timothy grass pollen extract and purified allergens, as well as significant IgG4 levels towards Phl p 1 (P = 0.000238) Phl p 2 (P = 0.000289), Phl p 4 (P = 0.000585), Phl p 5 (P = 0.000364), Phl p 6 (P = 0.000346) and Phl p 11 (P = 0.039623; Mann-Whitney U-test) 12 weeks after the onset of immunotherapy. The sera of seven of 11 subjects treated with calcium phospate-adsorbed grass pollen extract had significant IgG4 levels against Timothy pollen allergens, as well as significant IgG4 titers against Phl p 1 (P = 0.004703), Phl p 4 (P = 0.000282), Phl p 5 (P = 0.015480), Phl p 6 (P = 0.013012) and Phl p 11 (P = 0.005178). Patients treated with aluminum-adsorbed grass pollen extract had higher levels of IgG4 towards Phl p 2, 4 and 6 and natural Timothy grass extract compared with patients treated with calcium phosphate-adsorbed grass pollen extract. Both the alluminum-adsorbed and calcium phosphate-adsorbed grass pollen extract allergy vaccines induced significant titers of specific IgG4 towards Phleum pratense pollen extract (P = 0.008376 and 0.01148, respectively).
Conclusions: These results indicate that grass pollen immunotherapy elicits an array of antibody specificities that reflect the allergen content and the potency of allergen extracts; this could be of pivotal importance to define optimal allergen extract doses.

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Background: Because the mean lifespan is increasing and the percentage of elderly people among the population as a whole is also increasing, the management of elderly bronchial asthma patients will be an important issue in medicine in the future. In the present study, based on questionnaires given to 3224 asthmatic patients in Niigata Prefecture, the characteristics, management and circumstances of elderly asthmatic patients were investigated.
Methods: Questionnaires were completed by asthmatic patients and their physicians in participating institutions within Niigata Prefecture from September to October 1999. Patients more than 65 years of age were defined as elderly asthmatic patients and a comparison was made between these patients and younger asthmatic patients who were less than 64 years of age and were used as a control group.
Results: In the classification of bronchial asthma, a greater frequency of infectious and mixed-type bronchial asthma was found in the elderly, whereas the use of peak flow meters was lower in this group. Significant differences were found for both self-evaluation of the condition of the asthma and satisfaction with daily life between the two age groups. A lower incidence of ambulance use, emergency room visits and use of inhaled steroids was observed in elderly patients, although the incidence of hospital-ization and use of oral steroids was higher. The discrepancy between objective and subjective evaluation of asthma control, the incidence of the use of both inhaled and oral steroids and the low use of peak flow meters were problematic in the elderly.
Conclusions: Based on sufficient consideration of the problems specifically related to elderly asthmatic patients, adequate education and careful management of asthma in this group are required, and the accumulation of these steps will result in the achievement of the guidelines final goals.

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