Total serum IgE levels are associated with ambient ozone concentration in asthmatic adults

Background: Effects of air pollution exposure on IgE‐mediated response in asthmatics are poorly investigated. The aim was to examine the relationship between air pollution concentrations and total IgE levels in adult asthmatics. Methods: The present study relates to the 369 asthmatic adults from the French Epidemiological study on Genetics and Environment of Asthma (EGEA), with availability of data on both total serum IgE measurements and air pollution concentrations. Geo‐statistical models were performed on 4 × 4 km grids to assess individual outdoor air pollution exposure. Annual outdoor concentrations of ozone (O₃), nitrogen dioxide (NO₂), sulphur dioxide (SO₂), and particulate matter smaller than 10 μm size (PM₁₀), and concentrations of summer ozone were assigned to subject’s home address. Results: The geometric mean of total IgE was 161 IU/ml and the average of O₃ exposure was 44.9 ± 9.5 μg/m³. Ozone concentrations were positively related to total IgE levels and an increase of 10 μg/m³ of O₃ resulted in an increase of 20.4% (95% CI = 3.0–40.7) in total IgE levels. Adjustment for age, gender, smoking habits and previous life in the countryside did not change the results, and an increase of 19.1% (2.4–38.6) in total IgE was observed with O₃. Negative associations observed between NO₂ and total IgE levels disappeared after including O₃ in the models. Neither SO₂ nor PM₁₀ were correlated with total IgE levels. Conclusions: Results suggest that O₃ or related ambient pollutants may up‐regulate total IgE levels among asthmatic adults.     

The alpha-chain of high-affinity receptor for IgE (FcepsilonRIalpha) gene polymorphisms and serum IgE levels

BACKGROUND: The high-affinity receptor for immunoglobulin-E (IgE) (FcepsilonRI) plays a major role in the pathogenesis of allergy, but there are only two published studies on its alpha subunit (FcepsilonRIalpha) genetic variability in allergic diseases. AIMS OF THE STUDY: Mutational screening in the region of the FcepsilonRIalpha gene promoter and the first exon with subsequent genetic variability assessment in allergic patients and a random population sample. METHODS: Allergic subjects were individuals with asthma or urticaria. Age- and sex-matched controls were randomly selected from a large population sample. Mutational screening was performed using a single-stranded conformational polymorphism and subsequent sequencing. Detected polymorphisms were genotyped by restriction fragment length polymorphism. Total serum IgE was measured in allergic subjects and controls. Skin prick tests, blood eosinophil count and aspirin challenge test were performed only in the subjects. A subgroup of the subjects was further characterized by autologous serum skin test, histamine release test, Phadiatop and IgE antibodies against staphylococcal enterotoxins. RESULTS: Two linked polymorphisms -344 C>T and -95 T>C were found within the FcepsilonRIalpha gene. The allele -344 T frequency was 0.45 vs 0.37 (P = 0.33), and the allele -95 C frequency was 0.26 in subjects vs 0.30 in controls (P = 0.62). Serum IgE was significantly higher in subjects homozygous for the -344T allele (TT genotype) than in those carrying the -344 C allele (CT or CC genotype; P = 0.003), but this association was not detectable in controls. CONCLUSIONS: Our findings of genotype-related differences in IgE levels in allergic patients suggest an impact of -344 C>T but not -95 T>C gene polymorphism of FcepsilonRIalpha on total levels of IgE. The genetic variability in FcepsilonRIalpha at the -344 nucleotide of its regulatory sequence, though not related to atopy, predicts higher levels of the immunoglobulin.     

Filaggrin null mutations are associated with increased asthma exacerbations in children and young adults

Background:  Filaggrin ( FLG ) null mutations are important genetic predisposing factors for atopic asthma and have recently been shown to influence controller and reliever medication needs in asthmatic children. Our objective was to study the role of FLG null alleles in asthma exacerbations.
Methods:  FLG mutations R501X and 2282del4 were assayed in 1135 individuals ranging from 3 to 22 years old with asthma from Tayside and Dumfries, Scotland. Asthma exacerbations over the previous 6 months were also studied.
Results:  The FLG mutations were significantly associated with greater risk of exacerbations in children with asthma. Exacerbations were significant for the R501X but not the 2282del4 mutation and the combined genotype compared to the wild-type with odds ratios of 1.97 (95% CI, 1.19–3.22; P  = 0.009) and 1.61 (95% CI, 1.08–2.40; P  = 0.021), respectively. Individuals with FLG null alleles were more likely to require oral steroids (31.4% vs 19.5%; OR = 1.89; P  =   0.021) for their exacerbations. There was also a 1.71-fold increased risk (42.6% vs 30%; P  =   0.041) of school absence owing to asthma exacerbations in asthmatic individuals with FLG null mutation. On sub-group analysis, the effect of FLG mutations on asthma exacerbations is significant ( P  =   0.045) only for participants with relatively mild asthma controlled on inhaled steroids, with inhaled albuterol according to need.
Conclusion:  In addition to their effect on asthma medication requirements reported previously, there is an association between the presence of FLG null mutations and the risk of asthma exacerbations in asthmatic children and young adults.     

ADAM33 polymorphisms are associated with asthma susceptibility in a Japanese population

BACKGROUND: Asthma is the most common chronic disorder in childhood, and asthma exacerbation is an important cause of childhood morbidity and hospitalization. Asthma is believed to be a complex disorder involving genetic and environmental factors, and several asthma susceptibility loci have been identified through genome-wide screening. A disintegrin and metalloprotease 33 (ADAM33) was the first asthma susceptibility gene to be discovered by positional cloning in 2002. OBJECTIVE: The aim of the present study was to investigate whether single-nucleotide polymorphisms (SNPs) in ADAM33 are associated with childhood asthma in the Japanese population. METHODS: Twenty-three ADAM33 SNPs were genotyped by fluorescence correlation spectroscopy with the use of DNA from 155 families (538 members) identified through children with atopic asthma. The transmission disequilibrium test (TDT) was performed for family-based association study. RESULTS: TDT revealed that minor alleles of S+1, ST+4, and T2 SNPs were over-transmitted to asthma-affected offspring (P<0.05). According to the haplotype TDT, no haplotype of ADAM33 was transmitted preferentially to asthmatic offspring. CONCLUSION: Our results confirm the involvement of ADAM33 in the development of childhood asthma among the Japanese.     

Human dendritic cell 1 and dendritic cell 2 subsets express FcepsilonRI: correlation with serum IgE and allergic asthma

BACKGROUND: Type 1 dendritic cells (DC1) express the high-affinity IgE receptor (FcepsilonRI); however, the regulation of FcepsilonRI expression by DCs is not well understood. Type 2 DC (DC2) expression of FcepsilonRI has not been demonstrated. OBJECTIVE: We hypothesized that DC2 cellsalso express FcepsilonRI and that expression of FcepsilonRI by the DC1 and DC2 subsets correlates with serum IgE and allergic asthma disease status. METHODS: To test these hypotheses, we quantitated FcepsilonRI alpha chain expression by the peripheral blood precursor DC1 (pDC1) and pDC2 subsets by using flow cytometry. RESULTS: FcepsilonRI was expressed by the pDC1 and pDC2 subsets, as well as tissue DCs from tonsils. Relative FcepsilonRI expression by basophil, pDC1, and pDC2 subsets was 12:6.5:1, respectively. In both pDC subsets, FcepsilonRI expression was significantly greater in allergic asthmatic subjects than in nonatopic control subjects. pDC1 and pDC2 expression of FcepsilonRI was highly correlated to serum IgE concentration. The pDC1, pDC2, and basophil subsets demonstrated a similar magnitude of increase in FcepsilonRI expression relative to changes in serum IgE. CONCLUSIONS: FcepsilonRI expression is characteristic of both the DC1 and DC2 subsets. Furthermore, FcepsilonRI expression by these cells is highly correlated to serum IgE and to basophil FcepsilonRI expression and is greater in subjects with allergic asthma. These data support the concept that novel therapeutic approaches directly targeted at FcepsilonRI expression would affect both the sensitization and the effector phases of the allergen-specific immune response.     

The polymorphisms of Eotaxin 1 and CCR3 genes influence on serum IgE, Eotaxin levels and mild asthmatic children in Taiwan

BACKGROUND: Asthma is a complex disorder, which is known to be affected by interactions between genetic and environmental factors. The human Eotaxin 1 and CCR3 attract eosinophils and Th2-lymphocytes to migrate to the inflammatory foci that could represent a key mechanism in allergy and asthma. OBJECTIVE: We hypothesized that Eotaxin1 gene Ala23Thr and A-384 G, and CCR3 gene T51C polymorphisms are associated with plasma Eotaxin levels and predispose individuals to asthma pathogenesis. METHODS: One hundred seventy-eight hospital-based asthmatic children and 277 community-based controls aged from 5 to 12 years were recruited in southern Taiwan. Whole blood samples and questionnaires were collected. In this study, we addressed genetic effects of Eotaxin 1 and CCR3 genes on asthma, plasma IgE and Eotaxin 1 levels. RESULTS: In comparison with subjects with Ala23Ala genotype, Ala23Thr polymorphism of the Eotaxin 1 gene showed a significant protective effect on asthma (AOR = 0.58, 95% CI = 0.37-0.92). We demonstrated that the mean Eotaxin 1 concentration was significantly higher in subjects with Ala23Ala than in subjects with Thr23Thr (P = 0.005) or Ala23Thr (P = 0.07), which showed a gene-dose dependent relationship. But, we observed that the A-384G polymorphism of Eotaxin 1 gene and T51C polymorphism of CCR3 gene are not associated with asthma. CONCLUSION: This study finding provide a strong evidence that Eotaxin 1 Thr23Thr homozygote has a protective effect on asthma and significantly decreases plasma Eotaxin 1 concentrations in asthmatics in Taiwan.     

Association of interleukin 18 (IL18) polymorphisms with specific IgE levels to mite allergens among asthmatic patients

BACKGROUND: Allergy is regarded as a multifactorial condition. Its onset and severity are influenced by both genetic and environmental factors. Identification of genetic factors involved in asthma development and related phenotypes is a major task in understanding the genetic background of asthma. The possible involvement of IL18 polymorphisms in asthma was examined in a Korean asthma cohort. METHODS: Direct sequencing was performed to discover single-nucleotide polymorphisms (SNPs) in the IL18 gene. Single-base extension (SBE) method was employed for genotyping. Genotypic influence of IL18 was analysed using logistic and multiple-regression models. RESULTS: Although no polymorphisms in the IL18 gene showed significant association with the risk of asthma development, analyses of the association with specific serum IgE levels to Dermatophagoides farinae (D.f.) and D. pteronyssinus (D.p.) among asthmatic patients revealed significant associations with two completely linked SNPs, i.e. -148G>C and +13925A>C(Ser35Ser) (P = 0.01-0.11 for D.f. and P = 0.005-0.11 for D.p.). Both C allele of -148G>C and C allele of +13925A>C showed gene dose-dependent effects on the levels of specific IgE. The lowest IgE levels in homozygotes of minor alleles (1.13 and 1.22 of D.f.; 1.38 and 1.33 of D.p., respectively), intermediate IgE levels in heterozygotes (1.60 and 1.70 of D.f.; 1.84 and 1.92 of D.p., respectively), and the highest levels in homozygotes for major allele (1.93 and 1.93 of D.f.; 2.24 and 2.24 of D.p., respectively), were found. CONCLUSION: The genetic relevance of IL18 to specific IgE might offer an important step in understanding the genetic background of allergic diseases.     

IL-4 receptor alpha chain genetic polymorphism and total IgE levels in the English population: two-locus haplotypes are more informative than individual SNPs

The IL-4RA locus encodes for the alpha chain of the IL-4 receptor, and is both a functional and positional candidate gene for atopy and allergic disease. Recently Ober et al. have shown that the study of haplotypes at multiple loci in the IL-4RA gene could be more informative than the separate study of single nucleotide polymorphisms (SNPs). One hundred and fifty subjects affected by atopic asthma and 150 healthy control subjects were studied in the English population (Oxford district). Subjects and controls were genotyped for the Ile50Val, Ser478Pro and Gln551Arg polymorphism of the IL-4 receptor alpha chain. The distribution of haplotypes 50-478 shows a highly significant association with IgE levels. In particular, the haplotype Val50/Pro478 is much less frequent in subjects with IgE levels > 100 U mL-1 than in those with IgE levels < 100 U mL-1. Furthermore, the distribution of haplotype 50-551 shows a weak association with IgE levels that is lacking for 478-551 haplotypes. A lower frequency of the Val50/Pro478 haplotype is also observed among asthmatic subjects as compared to healthy controls. With regard to individual SNPs (50 478 and 551), no significant association has been observed with IgE levels or with asthma, thus confirming the higher informative value of the haplotype analysis as compared to separate study on SNPs.     

The relation of markers of fetal growth with asthma, allergies and serum immunoglobulin E levels in children at age 5–7 years

BACKGROUND: It has been suggested that fetal growth and maturation have an impact on the development of allergic diseases later in life. OBJECTIVE: To examine the association between measures of fetal growth and allergic disease in children at age 5-7 years. METHODS: As part of the German International Study of Asthma and Allergies in Childhood phase II surveys, a random sample of school beginners (n=1138) was examined in 1995. Data on anthropometric measures at birth and gestational age were obtained from maternal copies of birth records. Data on symptoms and doctor-diagnosed asthma, atopic dermatitis and hayfever were gathered by parental questionnaires. Atopic sensitization was assessed by serum IgE and skin prick tests to common aeroallergens. Children (741) had complete data for the explanatory variables of interest and were thus eligible for this analysis. Confounder-adjusted prevalence odds ratios (PORs) and means ratios with 95% confidence intervals (CI) were calculated using multiple logistic and linear regression. RESULTS: Birth weight and gestational age were positively associated with atopic sensitization (Ptrend=0.025 and 0.035, respectively). Children with a low birth weight relative to head circumference had a decreased risk of sensitization (POR 0.44, 95% CI 0.21-0.91; Ptrend=0.020). Moreover, total serum IgE increased with increasing birth weight (Ptrend=0.042). No consistent relationship was observed between markers of fetal growth and wheezing, doctor-diagnosed asthma, atopic dermatitis and hayfever. CONCLUSION: These data suggest that fetal growth and maturity are associated with atopic sensitization and total serum IgE levels in childhood.