Volume 116, Issue 1 , Pages 223-225, July 2005
Childhood cat exposure–related tolerance is associated with IL1A and IL10 polymorphisms
Article Outline
To the Editor:
Atopic parents have been advised not to acquire pets to reduce their child's risk of allergic diseases. However, it has been shown that the presence of a cat in the home might decrease the risk of sensitization to cat allergen,1 and exposure to domestic pets in the first year of life significantly reduces the risk of allergic sensitization in children.2, 3
IL-1 is a potent inducer of IL-10 and also plays a role in early T-cell priming, which has been considered to be one key point of interest in the development of tolerance.4 We have previously studied IL1A (G/T base exchange at +4845) and IL10 promoter region polymorphism in atopy and asthma.5, 6
Now we investigated whether the genes encoding the cytokines IL-1α (IL1A) and IL-10 (IL10) affect exposure-related tolerance. Therefore we analyzed the association of cat and dog exposure in childhood with the sensitization to cat and dog allergens in a population-based sample of adult asthmatic subjects (n
=245) and their nonasthmatic control subjects (n=405). Detailed information on the study population has been presented previously in this journal.5
Patients were considered to be exposed to cat, dog, or both if they answered yes to the following question: “Were you in the same room with a cat (dog) daily or almost daily in early childhood?” Sensitization to cat and dog was tested with the skin prick method, as described previously.5 The IL1A (+4845G>T) polymorphism and IL10 promoter region haplotypes (formed by −1082G>A, −819C>T, and −592C>A) were analyzed as previously described.5, 6 For frequency analyses, the IL-10 genotypes were further categorized to IL-10 high producer (GCC+; genotypes GCC/GCC, GCC/ATA, and GCC/ACC) and IL-10 low producer (GCC−; genotypes ACC/ATA, ACC/ACC, and ATA/ATA) groups on a biologic basis.7
As expected, asthmatic subjects had more often a parent with asthma or allergy than control subjects (32.1% vs 12.6%; P < .001, χ2 test; df=1). Daily exposure to cat (as well as to dog) in childhood was equally common in families with or without parental asthma or allergy (Table I). Neither of the childhood animal exposures studied was significantly associated with asthma. The number of positive reactions to cat allergen was markedly lower in asthmatic subjects with daily cat exposure in childhood when compared with nonexposed asthmatic subjects (Table I). The effect of cat exposure increased in asthmatic subjects with a family background of asthma or allergy (Table I). There were no significant associations between dog exposure in childhood and sensitization to dog in any of the groups (data not shown).
Table I. Prevalence of positive reactions to cat in skin prick tests in subjects with and without childhood exposure to cat
| Childhood exposure to cat | |||||||
|---|---|---|---|---|---|---|---|
| N | %Exp | Yes | No | P value | OR | 95% CI | |
| All asthmatic subjects | 241 | 58.1 | 17.1 | 28.7 | .032 | 0.51 | 0.28-0.95 |
| Asthmatic or allergic parent | |||||||
| Yes | 78 | 56.4 | 15.9 | 44.1 | .013 | 0.24 | 0.08-0.69 |
| No | 163 | 58.9 | 17.7 | 20.9 | .610 | 0.82 | 0.37-1.79 |
| All control subjects | 401 | 62.8 | 8.7 | 11.4 | .382 | 0.74 | 0.38-1.45 |
| Asthmatic or allergic parent | |||||||
| Yes | 50 | 64.0 | 12.5 | 33.3 | .077 | 0.29 | 0.68-1.20 |
| No | 351 | 62.7 | 8.2 | 8.4 | .944 | 0.97 | 0.44-2.13 |
In asthmatic subjects the protective effect was observed only in IL1A (+4845) allele G homozygotes (odds ratio [OR], 0.27; 95% CI, 0.10-0.72; P=.007; Fig 1) and in subjects with high IL-10 producer haplotype GCC (OR, 0.39; 95% CI, 0.19-0.82; P=.012; Fig 1). The strongest cat exposure–related protective effect against cat sensitization was found in the combined group of asthmatic and control subjects with a history of parental asthma or allergy. In this group (n=128) the prevalence of a positive reaction to cat allergen was 14.5% in exposed and 40.4% in nonexposed subjects (OR, 0.25; 95% CI, 0.11-0.58; P=.001). When the IL1A and IL10 polymorphisms were taken into the analyses, yet stronger associations were found in IL1A (+4845) allele G homozygotes (OR, 0.09; 95% CI, 0.02-0.31; P < .001; Fig 1) and IL10 haplotype GCC carriers (OR, 0.17; 95% CI, 0.060-0.49; P=.001; Fig 1).
Fig 1.
Proportion of cat-sensitized subjects with or without childhood exposure to cat in relation to IL1A (+4845G>T) genotype and IL10 haplotype GCC in asthmatic subjects (n
=239), in control subjects (n=396), and in all subjects (both asthmatic and control subjects) with a family history of allergy or asthma (n=128). P values were calculated with the χ2 test (df=1).
In our study we show for the first time that the IL1A and IL10 genes are substantially related to the development of cat exposure–induced tolerance. Because IL1A (+4845) G homozygosity and IL10 GCC carrier states are very common, these observations have a substantial effect on the risk of sensitization at the population level. Exposure-related tolerance is strongest in subjects reporting a family history of atopy.1, 8 IL1A (+4845) G homozygosity is more common in subjects with atopy,5 and it could be one of the factors that mediate the effect of family background.
It can be further concluded from our results that avoiding pets cannot be recommended as a preventive measure to avoid atopy. The associations of IL1A and IL10 illustrated in the present study indicate that exposure-related tolerance is a biologic phenomenon with demonstrable genetic background. It further remains to be elucidated whether the IL1A and IL10 genotypes mediate the responses in induced tolerance (ie, in immunotherapy).
References
- Role of current and childhood exposure to cat and atopic sensitization. J Allergy Clin Immunol. 1999;104:941–947
- . Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA. 2002;288:963–972
- Effects of dog ownership and genotype on immune development and atopy in infancy. J Allergy Clin Immunol. 2004;113:307–314
- . Paradoxical effect of domestic animals on asthma and allergic sensitization. JAMA. 2002;288:1012–1014
- The IL1A genotype associates with atopy in nonasthmatic adults. J Allergy Clin Immunol. 2002;110:429–434
- IL-10 gene promoter region polymorphism is associated with eosinophil count and circulating IgE in adult asthma. Clin Exp Allergy. 2003;33:78–83
- . Genetic association between interleukin-10 promoter region polymorphisms and primary Sjogren's syndrome. Arthritis Rheum. 2001;44:176–179
- . Effect of cat and dog ownership on sensitization and development of asthma among preteenage children. Am J Respir Crit Care Med. 2002;166:696–702
Supported by the Academy of Finland, the Rehabilitation Funds of the Finnish Social Insurance Institution, the Medical Research Fund of Tampere University Hospital, and the Tampere Tuberculosis Foundation.
PII: S0091-6749(05)00603-2
doi:10.1016/j.jaci.2005.03.026
© 2005 American Academy of Allergy, Asthma and Immunology. Published by Elsevier Inc. All rights reserved.
Volume 116, Issue 1 , Pages 223-225, July 2005
