Understanding of the Molecular Mechanisms of Allergy.

The prevalence of allergic disease has dramatically increased over the past 30 years in Westernized countries. It is unlikely that the rapid increase in the prevalence of allergic disease is the result of genetic changes, which highlights the importance of environmental factors in the development of allergic disease. The "hygiene hypothesis" was put forward in 1989 and focused attention on the notion that exposure to microbes and their products in early life can modify the risk for development of allergic disease. Infections were thought to polarize the immunological response toward a Th2-mediated immune response causing allergic disease. However, it is likely that the Th1/Th2 imbalance is too simplistic to explain the increased prevalence of allergic disease. Current research is focusing on understanding the role of T-regulatory cells in inducing a state of tolerance and the resulting modified Th2 response observed in natural and induced tolerance.

Measurement of Specific IgG Anti-Fel d 1 Antibodies.

There is currently considerable interest in the role of specific IgG antibodies in allergy. Several studies suggest that specific IgG antibodies may play a protective role in allergy. Successful immunotherapy is associated with increases in allergen-specific IgG antibodies which correlate with clinical outcome. Other studies have identified an inverse relationship between exposure to cat and sensitization, which was associated with high-titer-specific IgG and IgG4. This immune response was described as a modified Th2 response, since both IgE and IgG4 require Th2 cytokine IL-4 for their production. A modified Th2 response was described with laboratory animal allergy, where there was almost a twofold reduction in the risk of developing work-related chest symptoms.In this chapter, we review the major factors to be considered in the development of an ELISA for the determination of specific IgG and IgG4 antibodies.

Measurement of specific IgG anti-Fel d 1 antibodies.

There is currently considerable interest in the role of specific IgG antibodies in allergy. Several studies suggest that specific IgG antibodies may play a protective role in allergy. Successful immunotherapy is associated with increases in allergen-specific IgG antibodies which correlate with clinical outcome. Other studies have identified an inverse relationship between exposure to cat and sensitization, which was associated with high titer specific IgG and IgG(4). This immune response was described as a modified Th2 response, because both IgE and IgG(4) require Th2 cytokine IL-4 for their production. A modified Th2 response was described with laboratory animal allergy, where there was almost a twofold reduction in the risk of developing work-related chest symptoms.In this chapter, we review the major factors to be considered in the development of an ELISA for the determination of specific IgG and IgG(4) antibodies.

Exposure-response in occupational allergy.

PURPOSE OF REVIEW: This review examines the relationship between exposure to workplace allergens and the risk of developing occupational allergy. RECENT FINDINGS: Evidence suggests that the risk of developing occupational allergy increases with allergen exposure; however, with some occupational allergens, this exposure-response relationship is more complex. In laboratory animal workers, the risk of developing occupational allergy increases with exposure, except at high allergen exposure when there is a reduction in sensitization. This attenuation of specific immunoglobulin E antibody is associated with increased specific immunoglobulin G4 antibodies, which are likely to play a protective role, leading to a form of natural tolerance. Exposure-response relationships are also very dependent on the genetic susceptibility of the individual. The interaction between genes, occupational allergens and other cofactors in the environment, such as endotoxin, are also important risk factors in the development of sensitization and asthma. SUMMARY: Occupational allergy provides a good opportunity to understand the complex relationships between exposure to allergens in the workplace, interaction with genes and the coexposures with other factors in the working environment and the increased risk of developing occupational allergy.

Is occupational asthma to diisocyanates a non-IgE-mediated disease?

BACKGROUND: Exposure to diisocyanates in the workplace is an important cause of occupational asthma. The majority of patients with diisocyanate-induced asthma have no detectable diisocyanate-specific IgE antibodies in serum. There has been much debate as to whether this is due to diisocyanate-induced asthma being mediated by non-IgE mechanisms or whether it is the result of using inappropriate conjugates. OBJECTIVE: We sought to determine whether RNA message for Cepsilon, IL-4, and other associated inflammatory markers could be detected locally within the bronchial mucosa after diisocyanate challenge. METHODS: Fiberoptic bronchoscopic bronchial biopsy specimens were obtained at 24 hours after both a control and an active challenge in 5 patients with positive and 7 patients with negative inhalation test responses to diisocyanates. Using both immunohistochemistry and in situ hybridization, we determined mRNA for Cepsilon, IL-4, IL-5, and other associated inflammatory markers. RESULTS: There was a striking absence of Cepsilon and IL-4 mRNA-positive cells in bronchial biopsy specimens from patients challenged with diisocyanate (Cepsilon median of 0 and interquartile range of 0-1.85; IL-4 median of 0 and interquartile range of 0-0.85). In contrast, there were increased numbers of IL-5-, CD25-, and CD4-positive cells and a trend toward an increase in eosinophils after active challenge with diisocyanate. CONCLUSION: We found a striking absence of both bronchial Cepsilon and IL-4 RNA message after inhalation challenge with diisocyanates, irrespective of whether the challenge test response was positive or negative. We propose that diisocyanate-induced asthma is a non-IgE-mediated disease, at least in patients in whom specific IgE antibodies to diisocyanates are undetectable.