To develop new therapies for allergic diseases, novel target genes must be identified. There are three strategies in the research on identification of disease-related genes which could be candidates of novel target genes: 1) positional cloning based on linkage analysis of the disease phenotypes and marker genes; 2) identification of polymorphisms of a gene of known function that influences disease development, and a study on the relationship between particular polymorphisms and disease phenotypes; 3) exhaustive analysis of differentially expressed genes between patients and controls using a method of differential display (DD) or DNA arrays and so on. From the point of view that many atopic genes are involved in the development of allergic diseases, the third approach would be the most promising since the gene network underlying the disease could be identified.
Based on analysis of differentially expressd genes in T cells and eosinophils from allergy patients using the DD method, Genox Research Inc, has identified approximately fifty novel genes whose expression is correlated with various disease phenotypes.

View full abstract

Staphylococcus aureus frequently colonizes the eczematous skin of patients with atopic dermatitis (AD) and is thought to be an important precipitaing factor of AD. The mechanism of worsening AD by S aureus are thought to be that (1) superantigenic exotoxins act as superantigen and allergen, (2) cellular proteins of S aureus act as allergens, and (3) α-toxin and other cytolytic toxins directly destroy the skin tissue. These are the reason why elimination of S aureus is very important to treat AD.

View full abstract

Genetic factors, in conjunction with enviromental factors, are involved in the pathogenesis of allergic disorders. Extensive studies show that genetic factors may associate with the polymorphisms of the molecules responsible for IgE production and/or allergic reaction. Of such molecules, IL-4 Rα, a common component of the functional receptors for IL-4 and IL-13, is thought to be one of the atopy-causing genes, because the 150V substitution correlates with atopic asthma from both genetic and functional aspects. As allergic disorders are controlled by many genetic factors, further attempts shoud be made to identify other genes coordinating closely with the IL-4 Rα gene. Functional analysis of atopy-causing genes will contribute to the development of novel therapeutic procedures for allergic disorders.

View full abstract

Over the past decade, a number of cytokines with chemoattractive properties (chemokines) have been identified. These molecules have been found to possess a vast range of functions as embyogenesis, hematopoiesis, and inflammation. Eosinophils, major of f ector cells in allergic inflammation, ex-press a chemokine receptor, CCR 3, and ligands for CCR 3 induce various eosinophil functions. Of these ligands, eotaxin is the most important for eosinophils. Eotaxin expression is upregulated in tissue of allergic inflammation and the levels of its expression correlate with eosinophil infiltration and disease severity. Eotaxin is produced mainly by epithelial cells and f ibroblasts under the control of Th2 cytokines (upregulation) and Th1 cytokines (inhibition). Eotaxin exhibits such pleiotropic functions as myelopoiesis, eosinophil mobilization from bone marrow, eosinophil-endothelial cell adhesion, degranulation, and superoxide generation. Thus, eotaxin may be a “key player” in pathogenesis of allergic diseases.

View full abstract

Onset of food allergy usually starts from infancy. Diagnosis of food allergy during infancy could be made by the medical history, Prick skin test, IgE CAPRAST, food elimination test for two weeks, and food diary. However, it is necessary to perform food provocation tests for the cases sensitized with multiple allergens, and for the evaluation of the development of oral tolerance before starting school life. Currently, the treatment of food allergy is to eliminate food allergens, therefore, accurate diagnosis should be made by doctors. In some cases with food allergy, Double-Blind Placebo-Controlled Food Challenge (DBPCFC) is necessary to exclude the bias of both patients and doctors. Here we report the current consensus of diagnosis of food allergy and the establishment of food provocation test using dried food powder and strawberry pyre, with which DBPCFC could be easily carried out.

View full abstract

One of the treatment strategies for atopic diseases is to downregulate the Th2 system by inducing a Th1 response, because Th1 and Th2 cytokines are thought to be mutually antagonistic.
We reported that there was a strong association between tuberculin skin tests and atopic disorders. Positive tuberculin responses predicted a lower atopy, lower serum IgE level, and Th1 cytokine profiles.
Hopkin showed the evidence that injection of SRL 172 to patients with hay fever supprssed symptoms of lower respiratory tract.
And oter studies reported that administrations of BCG or SRL 172 suppressed Th2 system in OVA-sensitized mice.
These findings suggest that BCG should be effective in modulating allergic responses and may provided a therapeutic approach for atopic disorders.

View full abstract

DNA vaccination is a novel immunization technique to induce antigen-specific immune responses. This method is recognaized as an attractive approach not only for the vaccines of infectious disease, , but for treatment of cancer, autoimmune diseases and allergic diseases. Induction of allergen-specific Th1 cells by inoculation with plasmid DNA encoding gene of the sensitizing allergens suppresses the activity of Th2 cells, , which would be promising for interfering with the allergic reaction. It has become apparent that immune responses induced by DNA vaccination can be manipulated by altering the condition such as inculating method or route, , or coadministering adjuvant or plasmid DNA encoding gene of costimulatory molecules. In this review, we discuss the potential of DNA vaccination for the treatment of allergic diseases, including recent knowledge.

View full abstract