Elsevier

The Lancet

Volume 357, Issue 9258, 10 March 2001, Pages 752-756
The Lancet

Articles
Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study

https://doi.org/10.1016/S0140-6736(00)04168-4Get rights and content

Summary

Background

Although asthma is strongly associated with immediate hypersensitivity to indoor allergens, several studies have suggested that a cat in the house can decrease the risk of asthma. We investigated the immune response to cat and mite allergens, and asthma among children with a wide range of allergen exposure.

Methods

We did a population-based cross-sectional study of children (aged 12–14 years), some of whom had symptoms of asthma and bronchial hyper-reactivity. Antibodies to mite (Der f 1) and cat (Fel d 1) allergens measured by isotype (IgG and IgG4) specific radioimmunoprecipitation assays were compared with sensitisation and allergen concentrations in house dust.

Findings

226 children were recruited, 47 of whom had symptoms of asthma and bronchial hyper-reactivity. Increasing exposure to mite was associated with increased prevalence of sensitisation and IgG antibody to Der f 1. By contrast, the highest exposure to cat was associated with decreased sensitisation, but a higher prevalence of IgG antibody to Fel d 1. Thus, among children with high exposure, the odds of sensitisation to mite rather than cat was 4·0 (99% CI 1·49–10·00). Furthermore, 31 of 76 children with 23 μg Fel d 1 at home, who were not sensitised to cat allergen had >125 units of IgG antibody to Fel d 1. Antibodies to Fel d 1 of the IgG4 isotype were strongly correlated with IgG antibody in both allergic and non-allergic children (r=0·84 and r=0·66, respectively). Sensitisation to mite or cat allergens was the strongest independent risk factor for asthma (p<0·001).

Interpretation

Exposure to cat allergen can produce an IgG and IgG4 antibody response without sensitisation or risk of asthma. This modified T-helper-2 cell response should be regarded as a form of tolerance and may be the correct objective of immunotherapy. The results may also explain the observation that animals in the house can decrease the risk of asthma.

Introduction

The fact that sensitisation of asthmatic children reflects the allergens found in different climatic areas has been taken as evidence that exposure to allergens plays an important part in the disease.1, 2, 3, 4, 5, 6 For dust-mite allergens there is good evidence for a dose-response link between exposure and both sensitisation and asthma.1, 2, 7 By contrast, recent population-based studies have suggested that having a cat in the house could decrease the risk of sensitisation and asthma.8, 9, 10, 11 Simple explanations for this finding include the possibility that families affected by allergy avoid having animals in the house, or that the measurements of cat allergen do not adequately reflect exposure of the respiratory tract. An alternative explanation for the effect of animals in the home is that high amounts of animal products, such as antigens and endotoxins, can protect against the development of allergy. Thus, the effect of animals in the home could be seen as evidence for the hypothesis that increasing cleanliness has led to increased allergic disease because of a shift in the immune system from a T-helper-1 cell (Th1) to a T-helper-2 cell (Th2) bias.12, 13, 14, 15 However, research has shown that extended and high-dose exposure to occupational or injected allergens can induce an increase in IgG and IgG4 antibodies with a decrease in IgE antibodies,16, 17 and that expression of the gene for IgG4 can be induced by the Th2 cytokine interleukin 4 (IL-4).18, 19 Thus, a response including IgG4 without IgE antibody, could be regarded as a modified Th2 response. However, to date there has been no evidence that documents tolerance or any other form of immune response among non-allergic children with high exposure to one of the allergens associated with asthma.

In a population-based cross-sectional study of school children in the USA, we have previously reported that increasing concentrations of cat allergen (by contrast with mite allergen) did not increase the risk of sensitisation to cat allergen.3, 10, 20 In that study the children were exposed to a very wide range of dust mite (Der f 1 and Der p 1) or cat (Fel d 1) allergens. Subsequent analysis of that data has shown that the significant difference in the response to cat allergen was a decreased risk of sensitisation among children exposed to greater than 20 μg Fel d 1/g dust. This finding meant that there were a large number of atopic and non-atopic children who had documented high exposure to cat allergen but who were not allergic. The current study was designed to answer whether these children showed serological evidence of an immune response to Fel d 1. The results for isotype specific antibodies of children in our study were related to evidence of sensitisation, exposure, and the risk of asthma.

Section snippets

Methods

Children in grades seven and eight (age 12–13 years) of three middle schools were tested for lung function and answered a questionnaire in school. The schools were in Los Alamos, New Mexico; Albemarle County, Virginia; and Charlottesville, Virginia; and were chosen because they represent a wide range of climatic and socioeconomic conditions. On the basis of this screening children with symptoms or a history of asthma were identified.3, 10, 20 All the children identified as symptomatic by

Results

226 children were recruited to the study (117 boys, 109 girls), of whom 49 were African American and 47 had symptoms and BHR. Serum samples were available from all of them. Assessment of sensitisation to cat or mite allergen was based on RAST or skin tests because we wished to identify all the children who were allergic. In accordance with previous results, sensitisation to mite increased with increasing exposure1, 7, 22 (table 1). On examination the results and the published data we found that

Discussion

The immune response to common inhalant allergens includes IgG and IgA antibodies, as well as the IgE antibodies that give rise to sensitisation.23, 25 In all epidemiological studies the aspect of this immune response that had been used to investigate the association with asthma is immediate hypersensitivity judged by skin tests or serum IgE antibodies. Extended exposure, either naturally or during immunotherapy, can progressively increase the expression of the IgG4 isotype.16, 17, 26, 27 Our

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