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Notes: Background Influences of microbial pathogens are crucial for the maturation of the immune system. Caspase-recruitment domain containing protein 15 (CARD15) is a cytosolic receptor involved in bacterial recognition by antigen-presenting cells. CARD15 polymorphisms have been associated with Crohn's disease. Recently, associations with atopic phenotypes have been reported in children.Objective Within a large population of German adults (n=1875), we evaluated eight CARD15 polymorphisms for associations with atopic phenotypes.Methods Subjects were phenotyped by standardized questionnaires and interviews as well as total and allergen-specific IgE measurements. Genotyping was performed using matrix-assisted laser desorption ionization – time of flight mass spectrometry. Haplotypes were estimated using the SAS/Genetics module.Results Subjects with a T allele at rs1077861 had a decreased risk of developing asthma (odds ratio OR=0.648, P=0.013), whereas the presence of an A allele at rs3135500 was significantly associated with an increased risk (OR=1.374, P=0.023). In addition, a CARD15 haplotype revealed to be protective against the development of asthma (OR=0.326, P=0.003). Subjects with an A allele at position rs5743266 or a T allele at rs2066842 had a significantly decreased risk of developing allergic rhinoconjunctivitis with ORs of 0.820 (P=0.049) and 0.801 (P=0.025). Polymorphism rs2066845 showed a significant association with increased total serum IgE (OR=2.155, P=0.006).Conclusion Genetic variants of CARD15 that might result in inappropriate immunomodulation are not only associated with autoimmune diseases but also with atopic disorders.

Notes: Background:  Worm infestations may play a role in preventing allergies. There is a lack of epidemiological information from Western countries on the association between worm infestation and eczema.Objective:  To investigate the association between worm infestation and eczema in a proper temporal sequence and under consideration of allergic sensitization.Methods:  Two surveys were performed in East German school children. Questionnaire data included the history of eczema and worm infestation and their time of onset. Specific IgE antibodies to five common aeroallergens were measured and used to define nonatopic and atopic eczema. Logistic regression analyses were performed to control for relevant confounders (age, sex, parental school education and history of allergies). In order to confirm the findings a corresponding conditional regression analysis was applied on cases and controls matched by age and sex.Results:  A total of 4169 children participated (response 75 and 76%) who were, on average, 9.2 years old (47% girls). Overall 17.0% reported a prior worm infestation (Ascaris 44%, Oxyuris 33%) and 18.1% had a history of eczema. Eczema occurred significantly less frequent in children who had a worm infestation (prior to the onset of eczema) compared with children without such a history (8.1%vs 16.5%, ORadj: 0.45, 95% CI: 0.33–0.60). The finding was confirmed by the corresponding matched case–control analysis (ORadj: 0.57, 95% CI: 0.41–0.79). Atopic eczema was affected more by a prior worm infestation (ORadj: 0.31, 95% CI: 0.18–0.56) than the nonatopic eczema (ORadj: 0.58, 95% CI: 0.40–0.84). A total of 29.1% exhibited specific IgE antibodies to at least one aeroallergen. Sensitized children gave significantly less frequent a history of worm infestation (14.2%vs 18.3%, ORadj: 0.74, 95% CI: 0.60–0.92). Stratified analysis revealed that this effect most pronounced for a sensitization to house dust mite.Conclusions:  A worm infestation is associated with a reduced frequency of subsequent eczema, especially the atopic type. Furthermore allergic sensitization, especially to house dust mite, and worm infestation are negatively associated. The data support the concept that a lack of immune-stimulation by parasitic infections contributes to the development of allergies.

Notes: Background:  Atopic disorders are the result of complex interactions between genetic and environmental factors. Associations analyses between the promoter polymorphism rs1800875 in the mast cell chymase gene (CMA1) and atopy-related phenotypes have yielded inconsistent results.Methods:  We sequenced the CMA1 locus in 24 unrelated healthy individuals with serum IgE levels 〈50% percentile and 24 individuals with atopic eczema and serum IgE levels 〉90% percentile. Seven CMA1 single nucleotide polymorphisms (SNPs) were evaluated for evidence of associations with atopic phenotypes within a large population of German adults (n = 1875). Subjects were phenotyped by standardized questionnaires and interviews, skin prick testing and serum IgE measurements. Genotyping was performed using MALDI-TOF MS (Matrix-Assisted Laser Desorption Ionization–Time of Flight mass spectrometry).Results:  Promoter polymorphism rs1800875 was significantly associated with atopic eczema. No associations between any other single SNP and atopic phenotypes could be detected. Haplotype reconstruction revealed four of 128 possible haplotypes reaching estimated frequencies of 3% or more. Two of these haplotypes showed a borderline-significant association with atopic eczema, which did not remain significant after correction for multiple testing.Conclusions:  Results confirm previous observations of a significant association between the CMA1 promoter polymorphism rs1800875 and atopic eczema, but not with serum IgE levels, and support the hypothesis that CMA1 serves as candidate gene for atopic eczema.