Interleukin 13, CD14, pet and tobacco smoke influence atopy in three Dutch cohorts: the allergenic study

Bottema, R. W. B.; Reijmerink, Naomi E.; Kerkhof, Marjan; Koppelman, Gerard H.; Stelma, F.F.; Gerritsen, Jorrit; Thijs, Carel; Brunekreef, Bert; Schayck, C.P. van; Postma, Dirkje S.

doi:10.1183/09031936.00162407

Cited by 68 publications

(88 citation statements)

References 28 publications

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“…We replicated the association of the IL13-1111T variant reported by Howard et al (8) with a positive skin test and the association of IL13-1512C and IL13-1111T variants with atopy, defined as increased total serum IgE levels reported in three different allergic cohorts of more than 3000 children (18).…”

Section: Discussionsupporting

confidence: 74%

Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease

Beghè¹,

Hall²,

Parker³

et al. 2010

Allergy

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Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory respiratory diseases that are most likely due to an interaction between genetic and environmental factors. Atopy is the most important risk factor of asthma (1) and tobacco smoking is the most important risk factor of COPD (2).Interleukin-13 (IL13) is a Th2 cytokine implicated in (i) recruitment of inflammatory cells from the blood to the lung, (ii) immunoglobulin (Ig) E production by B cells, (iii) regulation of matrix metalloproteinases and (iv) induction of mucin production and secretion (3, 4). IL13 is produced by a variety of cells, including Th2 CD4 + , Th1 CD4 + , CD8 + T cells, mast cells, basophils and eosinophils. IL13 mediates its effects by interacting with a complex receptor system comprising an IL4Ra/IL13Ra1 heterodimer and the IL13Ra2 receptor (3).The involvement of IL13 in the pathogenesis of asthma has been extensively documented (3-5). The administration of recombinant IL13 in the lungs of mice increases airway AbstractBackground: Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases involving an interaction between genetic and environmental factors. Interleukin-13 (IL13) has been suggested to have a role in both asthma and COPD. We investigated whether single nucleotide polymorphisms (SNPs) in the IL13 pathway may contribute to the susceptibility and severity of asthma and COPD in adults. Methods: Twelve SNPs in IL13 pathway genes -IL4, IL13, IL4RA, IL13RA1, IL13RA2 and STAT6 -were genotyped in subjects with asthma (n = 299) and in subjects with COPD or healthy smokers (n = 992). Genetic association was evaluated using genotype and allele models for asthma severity, atopy phenotypes and COPD susceptibility. Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV 1 , FEV 1 /FVC). Results: In asthmatics, three IL13 SNPs -rs1881457(-1512), rs1800925(-1111) and rs20541(R130Q) -were associated with atopy risk. One SNP in IL4RA1 [rs1805010(I75V)] was associated with asthma severity, and several IL13 SNPs showed borderline significance. IL13 SNPs rs1881457(-1512) and rs1800925 (-1111) were associated with better FEV 1 and FEV 1 /FVC in asthmatics. IL13 SNPs rs2066960(intron 1), rs20541(R130Q) and rs1295685(exon 4) were associated with COPD risk and lower baseline lung function in the recessive model. In females, but not in males, rs2250747 of the IL13RA1 gene was associated with COPD and lower FEV 1 . Conclusion: These data suggest that IL13 SNPs (promoter and coding region) and, to a lesser extent, IL4RA SNPs may contribute to atopy and asthma. We also provide tentative evidence that IL13 SNPs in the coding region may be of significance in COPD susceptibility.

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Section: Discussionsupporting

confidence: 74%

Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease

Beghè¹,

Hall²,

Parker³

et al. 2010

Allergy

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“…Many studies have investigated the effect of pet keeping on the development of atopic diseases in children (2,38). Interestingly, our results showed significantly lower IgE levels in the serum of atopic pet owners than in atopics without pets (Figure 3).…”

Section: Discussionsupporting

confidence: 50%

“…As environmental factors such as pets and tobacco smoke exposure are associated with the development of atopy in children (2,16), and the relationship between sCD14 levels and environmental factors has been poorly investigated in atopic patients, understanding this relationship may be important for identifying the mechanisms that regulate IgE production.…”

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confidence: 99%

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Soluble CD14 and total IgE in the serum of atopic and nonatopic adolescents in relation to environmental factors: a pilot study / Topivi receptor CD14 i ukupni IgE u serumu mladih atopičara odrasle dobi u ovisnosti o čimbenicima iz okoliša: pilot istraživanje

Prester

Varnai

Macan

2015

Archives of Industrial Hygiene and Toxicology

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The CD14 receptor is expressed on the surfaces of monocytes, macrophages, and, to a lesser extent, of activated granulocytes and B lymphocytes (mCD14). It also exists in soluble form in the serum (sCD14), in which it binds microbial compounds and indoor allergens. The objectives of this study were to see whether serum sCD14 concentrations could be used as a marker of atopic disorders and to estimate the effects of environmental factors (tobacco smoke exposure, childhood residence in urban or rural areas, and having a pet) on sCD14 and IgE values. Mass fraction of sCD14 and total IgE were determined in the sera of atopic (N=53) and non-atopic (N=35) participants using the standard enzyme-linked immunosorbent assay. Exposure to pets and environmental tobacco smoke was estimated based on the International Study of Asthma and Allergies in Childhood questionnaire (ISAAC). Median sCD14 concentration was significantly lower in atopic than in non-atopic girls (3.49 vs. 3.83 μg mL -1 ; p<0.010). The number of smokers at home positively correlated with the sCD14 level in atopics, and urban atopics had significantly lower sCD14 levels than rural atopics (3.47 vs. 3.92 μg mL -1 , p=0.028). Median total IgE concentration was significantly lower in atopic pet owners than in atopics with no pets (161 vs. 252 kIU L -1 ; p=0.021). In conclusion, while sex and environmental factors might be involved in sCD14 expression, particularly in atopics, we found no correlation between sCD14 and total IgE concentrations. The usefulness of sCD14 as a marker of atopic disorders should be investigated further, particularly in relation to the severity of allergic disorders.KEY WORDS: allergy; atopy; environmental tobacco smoke; immunoglobulin E; sCD14; pets Prester Lj, et al. Soluble CD14 and total IgE in the serum of atopic and non-atopic adolescents in relation to environmental factors: a pilot study Arh Hig Rada Toksikol 2015;66:41-49

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“…Quality of genotype data was guaranteed by standards of K-Biosciences with extensive quality control as described before. 13 The genotype data of the healthy control subjects were analyzed for deviations from Hardy --Weinberg equilibrium using 1 degree of freedom chi-square tests. None of the SNPs deviated from HWE (Po0.01).…”

Section: Genotypingmentioning

confidence: 99%

Polymorphisms in the TLR6 gene associated with the inverse association between childhood acute lymphoblastic leukemia and atopic disease

et al. 2011

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Interleukin 13, CD14, pet and tobacco smoke influence atopy in three Dutch cohorts: the allergenic study

Cited by 68 publications

References 28 publications

Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease

Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease

Soluble CD14 and total IgE in the serum of atopic and nonatopic adolescents in relation to environmental factors: a pilot study / Topivi receptor CD14 i ukupni IgE u serumu mladih atopičara odrasle dobi u ovisnosti o čimbenicima iz okoliša: pilot istraživanje

Polymorphisms in the TLR6 gene associated with the inverse association between childhood acute lymphoblastic leukemia and atopic disease

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