Search

Summary Objective The aim of our study was to conduct a prospective investigation into the potential association of cord blood proliferative response and cytokine production in response to various stimuli on the development of atopic dermatitis (AD) at the age of 3 years. Methods Cord blood mononuclear cells (CBMC) from 40 healthy term neonates were isolated. The proliferative response of CBMC stimulated with IL-2, betalactoglobulin (BLG) and house dust mite allergen (Der p 1) was assessed by liquid scintillation counting and the stimulation index (SI) was calculated. The cytokines interleukin (IL-)13, interferon (IFN-)γ, IL-10 and IL-18 in the cell culture supernatants in response to phytohaemagglutinin (PHA), Der p 1 and BLG were measured using the ELISA technique. After 3 years, symptoms of AD were obtained with a questionnaire completed by the parents. Results We observed significantly higher IL-13 levels in response to PHA in children who subsequently developed symptoms of AD (S: median, 291 pg/mL) compared with asymptomatic children (No-S: 149 pg/mL; P=0.021, Wilcoxon test). Similarly, in response to Der p 1 significantly higher IL-13 levels were observed in symptomatic children (S: 168.6; No-S: 61.6 pg/mL; P=0.0084). In response to BLG, IL-13 levels were 287.2 (S) and 123.6 pg/mL (No-S; P=0.19). No significant differences were found when comparing the IFN-γ levels in CBMC cultures stimulated with PHA (S: 10.2; No-S: 17.6 IU/L; P=0.78), Der p 1 (S: 307.6; No-S: 616.2 IU/L; P=0.2) or BLG (S: 18; No-S: 28.5 IU/L; P=0.83; Fig. 2). The IL-18 and IL-10 levels and the stimulation index in response to IL-2, BLG and Der p 1 showed no significant difference between children who subsequently developed symptoms of AD and asymptomatic children. Figure 2. Release of interferon-gamma (IFN-γ) in response to phytohaemagglutinin (PHA), house dust mite allergen (Der p 1) and betalactoglobulin (BLG) in children who developed symptoms of atopic dermatitis at the age of 3 years (‘symptomatic’) and asymptomatic children. The median value and the 5th and 95th percentile are presented. Differences between the groups were calculated with the Wilcoxon test and P-values are reported. Conclusion Our data suggest that enhanced IL-13 levels at birth are associated with the subsequent development of atopic symptoms at the age of 3 years.

Background Successful pregnancy is dependent upon T helper (Th)2-type-dominated immunological responsiveness in gestation-associated compartments. Objective In our study we observed the influence of the maternal Th2-associated cytokine pattern on the naive fetal T cell phenotype and asked if circulating Th2 cytokines of atopic mothers affects the Th1/Th2 differentiation of the fetus. Methods Cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) of the corresponding mothers were isolated. The proliferative response of CBMC and PBMC to Betalactoglobulin (BLG) was assessed by liquid scintillation counting. The cytokines interferon (IFN)-γ, and interleukin (IL)-5, IL-10 and IL-13 in the cell culture supernatants were measured using the ELISA technique. We then defined two subgroups based on maternal levels of specific IgE against aeroallergens: sensitized mothers (MA+) and their neonates (NMA+) (n = 18) and non-sensitized mothers (MA−) and their neonates (NMA−) (n = 29). Results Nearly all mothers (98%) and neonates (92%) had a positive proliferation response after stimulation with BLG (mean stimulation index (10–90 percentile): neonates: 7 (2–15); mothers 14 (5–29)). In supernatants of BLG-stimulated cell cultures, sensitized mothers showed a significantly lower IFN-γ concentration in comparison to non-sensitized mothers (MA+ = 25; MA− = 123 IU/L; P

Background It is suggested that urinary eosinophil protein X (EPX) is a noninvasive tool to monitor bronchial inflammation in asthmatic children. However, circadian variation of the number and activation of eosinophils might possibly influence urinary EPX excretion. Objective Measurements of urinary EPX (radioimmunoassay) were used to investigate circadian variation of eosinophilic activation and to monitor bronchial inflammation in children with asthma before and after treatment with corticosteroids. Methods Urinary EPX excretion (μg/mmol creatinine) was measured in the morning and afternoon in 22 stable asthmatics and in 16 nonatopic, nonasthmatic controls to investigate circadian variation. Additionally, EPX excretion in the afternoon was analysed in 21 children with chronic asthma before and after 6 weeks of treatment with inhaled corticosteroids, and in seven children within 24 h of admission due to an asthma exacerbation and again 3 months after discharge. Results EPX excretion in the first morning urine sample of the day compared with the afternoon urine sample was significantly higher both in children with asthma (n = 22; mean ± standard deviation: 179.7 ± 97.3 vs 60.9 ± 40.7 μg/mmol creatinine, P = 0.0001) and in nonatopic nonasthmatic controls (n = 16; 114.5 ± 57.1 vs 53.4 ± 29.0 μg/mmol creatinine, P = 0.0001). EPX excretion decreased significantly after 6 weeks of anti-inflammatory treatment in the group of children with chronic asthma (n = 21; 124.7 ± 84.6 vs 87.5 ± 61.9 μg/mmol creatinine, P = 0.02) and in the group of children with an acute asthma exacerbation 3 months after discharge (n = 7; 233.2 ± 174.5 vs 75.8 ± 59.5 μg/mmol creatinine, P = 0.02). Conclusion This study suggests a circadian variation of EPX excretion in children with asthma and in nonatopic, nonasthmatic controls. Measurement of EPX excretion is helpful monitoring therapy in asthmatic children if circadian variation is considered.

Background IgE response to common inhalant allergens seems to be the major determinant of the development of atopic rhinitis and asthma but it has been difficult to demonstrate genetic control of the IgE response. Objective To investigate genetic linkage between specific IgE reactions to purified aero-allergens (grass, birch, cat, mite) and the HLA–class II locus. Methods DNA-based HLA–class II typing was performed for determination of DRB1, DQB1 and DPB1 alleles. Linkage was studied by the affected sibpair method and the extended transmission disequilibrium test in 100 children from 40 nuclear families selected from a homogeneous population in south-western Germany. Results Significant linkage of mite-specific IgE response to HLA–DPB (P = 0.00001), HLA–DRB (0.02) and HLA–DQB (P = 0.001) was revealed by sibpair analysis of MHC class II alleles and confirmed by the extended transmission disequilibrium test for HLA–DRB (P = 0.01) and HLA–DPB (P = 0.04). No consistent significant linkage between the HLA–class II locus and IgE response to grass pollen, birch pollen, and cat dander could be demonstrated. Conclusion The findings are consistent with the existence of one or more genes in the HLA–class II region modifying the IgE immune response to common environmental allergens.

Background Several studies have reported an association between a child's risk of atopic disorders and family size. However, the inverse association might not be the same in populations with a different genetic disposition for atopic disorders. Objective This longitudinal study was designed to assess risk factors of atopy. Methods Lifetime prevalence of asthma, hay fever and eczema of 1440 families including 3165 offspring was ascertained by means of standardized questionnaires. Results After possible confounders had been controlled for, an inverse association between atopic disorders and the number of older siblings was found only in the offspring of atopic fathers (trend for older siblings: χ2 = 13.38, degrees of freedom [d.f.] = 1, P = 0.0002; odds ratio ‘no older sibling’ = 2.87 (95% confidence interval 2.18–3.78); ‘1 older sibling’ = 2.11 [1.52–2.92], ‘2 older siblings’ = 1.29 [0.74–2.23]; ‘3 or more older siblings’ = 0.15 [0.02–0.98]). No such relationship was found for children without a history of paternal atopy (trend for older siblings: χ2 = 1.51, d.f. = 1, P = 0.22; odds ratio ‘no older sibling’ = 1 [reference]; ‘1 older sibling’ = 0.82 [0.63–1.06]; ‘2 older siblings’ = 0.97 [0.67–1.40]; ‘3 or more older siblings’ = 0.64 [0.31–1.33]). The trend for older siblings in the case of paternal atopy was significantly different from the trend for older siblings without a history of paternal atopy (χ2 = 8.68, d.f. = 1, P = 0.003). The number of younger siblings was not related to child's risk of atopy (trend for younger siblings: χ2 = 0.001, d.f. = 1, P = 0.97). Conclusions Data from this study suggest a protective effect of sibship size only in children with a history of paternal atopy and if older siblings are present. The reason for this combined effect remains unclear. Thus, further investigations are needed to interpret the biological cause of the so called ‘sibling effect’.

Background Atopy, a clinical syndrome characterized by heightened IgE responsiveness, is largely determined by genetic factors. The disease may well be heterogeneous but the mode of inheritance is unknown. Several genes have been named which affected IgE responsiveness. However, results are conflicting reflecting heterogeneity and a complicated inheritance pattern of the atopic syndrome. In 1994 linkage of the 5q32 gene region and elevated total IgE levels were reported, leaving the IL4 gene as a prominent candidate. Objectives We were interested in a possible involvement of the IL4-receptor gene in the development of atopy. Methods We employed sib-pair linkage analysis using highly polymorphic microsatellite markers within and flanking the IL4 receptor gene in atopic families, characterized for specific sensitization to inhalant allergens and elevated total serum IgE. Allele sizes were determined for all microsatellite probes to allow transmission disequilibrium analysis. Results We found significant sharing of maternal but not paternal alleles in affected sibs from two independent populations, both of which presented enhanced IgE responsiveness. Linkage and maternal inheritance could be confirmed by transmission disequilibrium analysis. Conclusions We conclude from our findings that maternal inheritance of a gene in the chromosome 16p12 region increases the risk for enhanced IgE responsiveness. The most prominent candidate in this region is represented by the IL4 receptor gene.