IgE responses to environmental antigens in atopic children

The levels of IgE antibodies to inhaled and dietary antigens and total serum IgG, IgA, IgM and IgE were studied in two highly selected populations of children who had either severe asthma and no history of eczema, or severe asthma and generalized eczema. These populations were age-matched with a healthy control population. The results showed that the eczematous children had significantly higher levels of IgE antibodies to common environmental antigens than the non-eczematous patients with severe asthma. Both patient groups had significantly higher IgE antigen specific antibody levels than the control population to these antigens. Minor differences in total IgG, IgA and IgM levels were noted between the groups. The variations in total IgE levels between the groups showed the same pattern as for specific IgE antibodies.     

Parental tobacco smoking is associated with augmented IL-13 secretion in children with allergic asthma

BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been shown to increase symptoms of allergic bronchial asthma, but direct effects on the expression of inflammatory markers have not been demonstrated thus far. OBJECTIVE: The aim of this study was to assess the correlation of ETS exposure with the expression of proinflammatory mediators in airway secretions, including IFN-gamma and IL-12, as well as IL-5 and IL-13, in allergic asthmatic schoolchildren and healthy control subjects. METHODS: By using the nasopharyngeal aspiration technique, airway secretions were collected from 24 atopic children with asthma (age, 6-16 years) and 26 healthy control subjects, and the concentration of cytokines was measured with immunoenzymatic methods. RESULTS: IL-13 levels were highly increased in patients with asthma (P < .005), and parental tobacco smoke resulted in a significant increase in airway IL-13 secretion in these children compared with that seen in nonexposed children and healthy control subjects (median, 860 pg/mL vs 242 pg/mL and 125 pg/mL, respectively). Furthermore, a positive correlation between IL-13 levels and serum IgE concentrations (r(s) = 0.55) was found in children with allergic asthma. CONCLUSIONS: These results indicate that ETS augments the expression and secretion of IL-13 in allergic asthma and that nasopharyngeal aspiration is a suitable method to assess cytokine measurements in airways in children. Measurements of IL-13 in secretions might be taken into account as a noninvasive marker of airway inflammation and to assess the detrimental effects of ETS.     

The relationship between vaccine refusal and self-report of atopic disease in children

BACKGROUND: In the last 3 decades, there has been an unexplained increase in the prevalence of asthma and hay fever. OBJECTIVE: We sought to determine whether there is an association between childhood vaccination and atopic diseases, and we assessed the self-reported prevalence of atopic diseases in a population that included a large number of families not vaccinating their children. METHODS: Surveys were mailed to 2964 member households of the National Vaccine Information Center, which represents people concerned about vaccine safety, to ascertain vaccination and atopic disease status. RESULTS: The data included 515 never vaccinated, 423 partially vaccinated, and 239 completely vaccinated children. In multiple regression analyses there were significant ( P < .0005) and dose-dependent negative relationships between vaccination refusal and self-reported asthma or hay fever only in children with no family history of the condition and, for asthma, in children with no exposure to antibiotics during infancy. Vaccination refusal was also significantly ( P < .005) and negatively associated with self-reported eczema and current wheeze. A sensitivity analysis indicated that substantial biases would be required to overturn the observed associations. CONCLUSION: Parents who refuse vaccinations reported less asthma and allergies in their unvaccinated children. Although this relationship was independent of measured confounders, it could be due to differences in other unmeasured lifestyle factors or systematic bias. Further research is needed to verify these results and investigate which exposures are driving the associations between vaccination refusal and allergic disease. The known benefits of vaccination currently outweigh the unproved risk of allergic disease.     

Polyclonal and allergen-induced cytokine responses in children with elevated immunoglobulin E but no atopic disease

BACKGROUND: Reduced Th1 and elevated Th2 cytokine responses are considered to be a principal mechanism in the generation of the inflammation leading to the manifestations of atopic disease in the skin of atopic dermatitis and in the airways of asthma. If reduced Th1 and elevated Th2 responses are principal determinants of the manifestation of atopic disease it might be expected that subjects with established disease would exhibit differences in their cytokine profiles as compared with atopic patients without clinical disease. OBJECTIVE: To determine whether asymptomatic atopic children exhibit a cytokine imbalance similar to that seen in patients with established atopic disease or if they behave like non-atopic controls. Cytokine responses in a group of children with elevated IgE but no clinical manifestations of disease, atopic children with established disease and non-atopic controls were compared. METHODS: We examined allergen-induced (house dust mite, HDM, rye grass pollen and RYE) cytokine responses in parallel with polyclonal (staphylococcal enterotoxin B, SEB) cytokine responses in a group of children with elevated serum IgE levels without current or past evidence of atopic disease (median age 6.6 years) and compared these with a non-atopic control group (median age 6.5 years) and a group of children with atopic disease (median age 6.7 years). RESULTS: Symptomatic atopic children had reduced SEB-induced IFN-gamma and increased SEB-induced IL-4 and IL-5 as compared with non-atopic controls. In contrast, SEB-induced IFN-gamma, IL-4 and IL-5 production in asymptomatic atopics was not significantly different from the non-atopic control subjects. Allergen-induced Th1 (IFN-gamma) and Th2 (IL-5 and IL-13) cytokine production was increased in both symptomatic atopics and asymptomatic atopics when compared with non-atopic controls. CONCLUSION: The defect in polyclonally induced IFN-gamma production was associated with the clinical manifestation of atopic disease but not the atopic stateper se. This suggests that the global reduction in IFN-gamma is the key determinant of the development of overt atopic disease. In contrast, elevated allergen-induced Th2 cytokine responses in children related to the atopic state per se irrespective of the presence of clinical atopic disease.     

Anticardiolipin antibodies in children with atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial etiology. Immunological abnormalities (cell-mediated immune hyperactivity, elevated IgE serum levels and eosinophil-derived mediators) have been observed. In a recent issue, Szakos et al. describe, in children with extrinsic type of AD, an association between the occurrence of anticardiolipin (ACL) IgM and specific IgE against mite, and also in relation to the severity of the disease. We studied 51 children (35 males and 16 females, mean age 44 months) with AD, whose diagnosis was made on the basis of Hanifin and Rajka's criteria. The evaluation of the severity of the disease was made using the SCORAD index. Eleven children had intrinsic type AD (group A); 40 children had extrinsic type AD, 14 of them had specific IgE only against food allergens (group B); 26 children had specific IgE also against inhalant allergens (group C). Twelve children without allergy were designated as the control group. Specific IgEs were determined using the CAP-System (Pharmacia, Uppsala, Sweden) for food and inhalant allergens. The measurement of ACL IgG and IgM was carried out by ELISA (Orgentec Diagnostika, Mainz, Germany). An increase in serum levels of ACL was observed in 13 children (25.5%): 1 child (9%) from group A, 7 children (50%) from group B and 5 children (19.2%) from group C with a statistically significant difference (P=0.038). Our study shows the presence of ACL-IgG above all in extrinsic AD, but no association was found between high levels of ACL and increased severity scoring of AD. Increased levels of ACL were observed in younger children (mean age 26.5 months; P=0.025) especially if sensitized against food allergens.     

Serum IgD concentrations in children with atopic diseases

When serum IgD was measured by electroimmunodiffusion (EID) in 60 children with atopy and in 55 normal children, the children with atopy had a mean serum IgD level of 2.47 mg. per 100 ml. and a standard error of the mean of 0.32 mg. per 100 ml. In contrast, the control group of normal children had a mean level of 3.59 ± (S.E.M.) 0.48 mg. per 100 ml. This difference was not statistically significant. IgD levels in the two groups could not be correlated with sex or diagnosis, but there was a significant (p < 0.05) correlation with age in the group with atopy. Further statistical analysis indicated that the lower mean IgD level in the atopic group was related to the lower mean age in this group. The study also demonstrated that EID is more sensitive than single radial diffusion (SRD) for the measurement of IgD in the serum of normal and atopic children.     

Epstein-Barr virus antibodies in children with atopic disease

The prevalence and titers of antibodies to human herpetoviruses as well as rubella and mumps viruses were determined in 98 children with atopic diseases and in 55 nonatopic control children. The only significant difference between the two groups was found as regards Epstein-Barr virus (EBV) antibodies, which were found in higher titers in atopic children of all ages. Increased levels of EBV antibodies were found both in children with asthma and atopic dermatitis. The frequency of seropositivity for EBV was slightly higher in atopics than in controls in all age-groups, but the differences observed were not statistically significant. The possibility that EBV, which is a B-cell mitogen, has a pathogenic role in the hyperproduction of IgE and development of atopic disease, should be considered.     

The FcgammaRIIa polymorphism in children with atopic diseases

BACKGROUND: Fcgamma receptor II (FcgammaRIIa) is the most widely distributed of the classes of FcR and is expressed in polymorphic forms on most types of hematopoietic cells. Recent data suggest that this polymorphism may be relevant to FcgammaRIIa function. This might be linked to variability in immune response and therefore related to the pathogenesis of atopic diseases. The aim of the study was to evaluate the FcgammaRIIa polymorphism in children with atopic diseases. METHODS: In the study were included 140 atopic children, 77 with food allergy and 126 healthy subjects as the control group. The FcgammaRIIa polymorphism was determined using the polymerase chain reaction method. RESULTS: The distribution of FcgammaRIIa genotypes in atopic children did not differ from that of healthy controls. Moreover, there was no association between the FcgammaRIIa genotypes and atopic diseases. CONCLUSION: It seems that the FcgammaRIIa polymorphism does not represent an important genetic risk factor for atopic diseases susceptibility.     

Clinical effects of probiotics are associated with increased interferon-γ responses in very young children with atopic dermatitis

BACKGROUND: We recently demonstrated that administration of probiotics resulted in significant clinical improvement in very young children with moderate-to-severe atopic dermatitis (AD). The purpose of this study was to determine the underlying immunological effects that are associated with these apparent clinical benefits. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from children (n = 53) at baseline and at the end of an 8-week supplementation period during which they received a probiotic (Lactobacillus fermentum PCCtrade mark) (n = 26) or a placebo (n = 27). A further sample was collected at 16 weeks (8 weeks after ceasing the supplement). Cytokine (IL-5, IL-6, IL-10, IL-13, IFN-gamma and TNF-alpha) responses to allergens (egg ovalbumin (OVA), beta lactoglobulin (BLG), house dust mite (HDM)), vaccines (tetanus toxoid (TT)), diphtheria toxoid (DT)), intestinal flora (heat-killed Lactobacillus (HKLB)), heat-killed Staphylococcus aureus (HKSA), Staphylococcus aureus enterotoxin B (SEB) and mitogen (phytohaemaglutinin (PHA)) were compared. RESULTS: The administration of probiotics was associated with a significant increase in T-helper type 1(Th1-type) cytokine IFN-gamma responses to PHA and SEB at the end of the supplementation period (week 8: P = 0.004 and 0.046) as well as 8 weeks after ceasing supplementation (week 16: P = 0.005 and 0.021) relative to baseline levels of response. No significant changes were seen in the placebo group. The increase in IFN-gamma responses to SEB was directly proportional to the decrease in the severity of AD (r = -0.445, P = 0.026) over the intervention period. At the end of the supplementation period (week 8) children receiving probiotics showed significantly higher TNF-alpha responses to HKLB (P = 0.018) and HKSA (P = 0.011) but this was no longer evident when supplementation ceased (week 16). Although IL-13 responses to OVA were significantly reduced in children receiving probiotics after 8 weeks (P = 0.008), there were no other effects on allergen-specific responses, and this effect was not sustained after ceasing supplementation (week 16). There were no effects on vaccine-specific responses, or on responses to any of the stimuli assessed. CONCLUSION: The improvement in AD severity with probiotic treatment was associated with significant increases in the capacity for Th1 IFN-gamma responses and altered responses to skin and enteric flora. This effect was still evident 2 months after the supplementation was ceased. The lack of consistent effects on allergen-specific responses suggests that the effects of probiotics may be mediated through other independent pathways, which need to be explored further.     

Clinical symptoms and IgE responses to common food proteins in atopic and healthy children

The appearance of symptoms suggestive of allergy through the first 4 years of life was studied prospectively in eighty-six healthy newborn babies. Blood samples were obtained at birth, at 3,8,25 and 48 months of age and analyzed for levels of total serum IgE and for IgE antibodies to some common foods. The occurrence of IgE antibodies was related to atopic manifestations and to a detailed history of infant feeding and family history of allergy. All infants with elevated cord blood IgE (more than 1.3 kU/1) developed manifestations of atopy. Specific IgE antibodies against egg, cow's milk and soy were demonstrated at 3, 8, 25 and 48 months in nine, twenty-three, six and two children respectively. Egg was a more potent sensitizing agent than cow's milk, IgE antibodies to egg being present in thirty-one samples, to cow's milk in eleven and to soy in five samples. Nine infants developed IgE antibodies to eggs or cow's milk before the introduction of these nutrients into the food. The IgE antibody levels were generally low in healthy non-atopic children and did, with one exception, not reach RAST class 1. In contrast, the levels of IgE antibodies to egg or cow's milk were higher in eleven blood samples from atopic children. We conclude that transient low IgE antibody responses to food proteins appear relatively often even in healthy infants. High concentrations of IgE antibodies however are almost exclusively seen in infants with atopic disease. Sensitization may appear early in infancy sometimes even before the offending food has been introduced into the diet.     

Experience with an elimination diet in children with atopic dermatitis

In order to define possible food-provoking factors, we placed twenty-nine children with chronic atopic dermatitis on an elimination diet. The children remained on their normal diet for 2 weeks followed by 2 weeks on the elimination diet. Foods were then re-introduced at the rate of a new one every 2 days in an attempt to identify foods exacerbating eczema. Thirteen children (45%) completed the elimination diet and seven of these were improved on parental assessment of sleeplessness, itchiness and area of eczema. Five were improved on the dermatologist's assessment. Only two children were able to identify foods provoking their eczema. Sixteen children (55%) failed to complete the elimination diet. Eight felt it was too strict, while eight did not return for follow-up. From our experience, dietary manipulation in older children with chronic atopic dermatitis offers only limited long-term therapeutic gains.     

Sleep and nighttime pruritus in children with atopic dermatitis

The number of scratching episodes and average frequency with which they started during each sleep stage as well as the effects of nighttime pruritus on objective sleep parameters in nine children with atopic dermatitis were assessed in the sleep laboratory. Scratching episodes occurred during rapid eye movement (REM) sleep and non-REM (NREM) sleep. The largest average frequency corresponded to stage 1, followed by stage 2, REM sleep, stage 4, and stage 3. Sleep maintenance was markedly altered. Total sleep time decrease was related mainly to smaller amounts of stage 4 NREM sleep. REM sleep percentage of total sleep time was increased as compared with normal children of the same age. Furthermore, in six of nine patients REM sleep latency was found to be decreased.     

Effect of climatic change in children with atopic eczema

BACKGROUND: Climate and sunlight (ultraviolet radiation) influence activity of atopic eczema. OBJECTIVE: To evaluate the effect of moving from a subarctic/temperate climate to a sunny subtropical climate on children's atopic eczema. METHODS: Children, 4-13 years, with severe atopic eczema were randomized to stay 4 weeks in Gran Canary (index patients = 30) and home in Norway (controls = 26), with a follow up of 3 months. SCORing of Atopic Dermatitis (SCORAD) was primary variable, and secondary were Children's Dermatology Life Quality Index (CDLQI), Staphylococcus aureus skin colonization and pharmacological skin treatment. RESULTS: SCORing of Atopic Dermatitis decreased from 37.2 (29.4-44.9) to 12.2 (9.0-15.4) [mean (95% confidence intervals)] after 4 weeks and 21.2 (17.2-25.1) 3 months thereafter in index patients (P < 0.0005), much less in controls.Children's Dermatology Life Quality Index in the index group improved from 8.7 to 2.2 and 4.5 after 4 weeks and 3 months (P < 0.0005), not in controls. Bacterial skin colonization with S. aureus decreased in the index group from 23/30 (77%) to 12/30 (40%; P = 0.001) and 12/30 (40%; P = 0.005) after 1 month and 3 months, and the use of local steroids decreased in index patients but not in controls. CONCLUSIONS: The change from a subartic/temperate to a subtropical climate for 4 weeks improved significantly skin symptoms (SCORAD) and quality of life, even for 3 months after return.