Library

Notes: The cross-reactivity of IgE antibodies is of interest for various reasons, three of which are discussed. Firstly, from the clinical view, it is important to know the patterns of cross-reactivity, because they often (but not always) reflect the pattern of clinical sensitivities. We discuss the cross-reactivities associated with sensitization to pollen and vegetable foods: PR-10 (Bet v 1-related), profilin, the cross-reactive carbohydrate determinant (CCD), the recently described isoflavone reductase, and the (still elusive) mugwort allergen that is associated with celery anaphylaxis; cross-reactivities between allergens from invertebrates, particularly tropomyosin, paramyosin, and glutathione S-transferase (GST); and latex-associated cross-reactivities. Clustering cross-reactive allergens may simplify diagnostic procedures and therapeutic regimens. Secondly, IgE cross-reactivity is of interest for its immunologic basis, particularly in relation to the regulation of allergic sensitization: are IgE antibodies to allergens more often cross-reactive than IgG antibodies to “normal” antigens? If so, why? For this discussion, it is relevant to compare not only the structural relation between the two allergens in question, but also the relatedness to the human equivalent (if any) and how the latter influences the immune repertoire. Thirdly, prediction of IgE cross-reactivity is of interest in relation to allergic reactivity to novel foods. Cross-reactivity is a property defined by individual antibodies to individual allergens. Quantitative information (including relative affinity) is required on cross-reactivity in the allergic population and with specific allergens (rather than with whole extracts). Such information is still scarce, but with the increasing availability of purified (usually recombinant) allergens, such quantitative information will soon start to accumulate. It is expected that similarity in short stretches of the linear amino-acid sequence is unlikely to result in relevant cross-reactivity between two proteins unless there is similarity in the protein fold.

Notes: Background: IgE-dependent histamine-releasing factor (HRF) can distinguish between IgE+ and IgE−. In contrast to IgE−, IgE+ sensitizes basophils to release histamine in response to HRF. But we do not know what particular feature distinguishes IgE+ from IgE−. The objective was to investigate the hypothesis that IgE+ is polymeric IgE. Methods: IgE+plasma was separated by size-exclusion chromatography. The basophil-sensitizing capacity of the fractions was analyzed in response to HRF produced by mononuclear cells. Results: We showed that monomeric IgE sensitized basophils to release histamine in response to HRF and to house-dust mite, whereas no enhanced reactivity was found in the fractions containing polymeric IgE. Conclusions: HRF reacts with monomeric IgE, and not (exclusively) with polymeric IgE.

Notes: Background In children at high risk of inhalation allergy, food sensitization is associated with an increased risk for sensitization to inhalant allergens. Furthermore, this association was also found in a cross-sectional study.Objective To examine in a prospective study, whether levels of IgG to foods (i.e. mixture of wheat and rice, mixture of soy bean and peanut, egg white, cow's milk, meat, orange and potato) indicate an increased risk for the future development of IgE antibodies to inhalant allergens in a low-risk population and whether they can be used as predictors of the subsequent development of IgE antibodies in young, initially IgE-negative children.Methods Coughing children, aged 1–5, visiting their GPs, were tested for IgE antibodies to mite, dog and cat (RAST) and IgG (ELISA) to foods. All IgE-negative children were retested for IgE antibodies after two years. The IgG results (66 percentiles) of the first blood sample were compared to the RAST-scores of the second blood sample.Results After two years, 51 out of 397 (12.8%) originally IgE-negative children, had become IgE-positive for cat, dog and/or mite. An increased IgG antibody level to wheat-rice (OR = 2.2) and to orange (OR = 2.0) indicated an increased risk of developing IgE to cat, dog or mite allergens. In addition to IgG to a mixture of wheat-rice and orange; total IgE, breastfeeding, eczema as a baby and age were the most important predictors for the subsequent development of IgE to inhalant allergens.Discussion An increased IgG antibody level to a mixture of wheat-rice or orange, indicates an increased risk of developing IgE to cat, dog or mite allergens. This indicates that excessive activity of the mucosal immune system is present before IgE antibodies to airborne allergens can be demonstrated. Nevertheless, IgG to foods is not very helpful (with a positive predictive value of 16.5%, and negative predictive value of 90.6%) in identifying individual children at risk in clinical practice. However, besides other risk factors, IgG to wheat-rice and to orange could be useful as a screening test for studies in the early identification, i.e. before IgE antibodies can be detected, of children with an increased risk of developing IgE antibodies in the future.

Notes: Background Exposure to house dust mite (HDM) allergens can lead to the development of allergic complaints. Mattress covers seem to be an obvious option for lowering allergen exposure in sensitized individuals. Previous studies have shown that Dermatophagoides pteronissinus was the most prevalent HDM species in the Netherlands.Objective In the present study, we investigated the effect of mattress covers on Der p 1 and Der f 1 concentrations in dust samples in three areas in the Netherlands; Groningen, Utrecht and Rotterdam.Methods Dust was obtained from mattresses of 277 patients at the beginning of the study and after 12 months of the placebo-controlled intervention. It was analysed for allergen content by immunoassay. The differential effect of the intervention on Der p 1 vs. Der f 1 was analysed in a subgroup with Der p 1+Der f 1〉1 μg/g dust (N=161). It was tested whether the intervention caused a significant change in the Der f 1/Der p 1 ratio.Results At t=0 we found very similar levels of the group 1 allergens of both species. The relatively high prevalence of D. farinae in our study was geographically restricted: the median Der f 1/Der p 1 ratio was 11.1 in the Rotterdam area compared with 1.32 in the Utrecht area and 0.33 in the Groningen area. Analysis of our data showed that the favourable intervention effect found for the combined allergen data (reduction factor=2.9, P〈0.001) is essentially due to a favourable effect of the intervention on the Der f 1 levels only (reduction factor=3.6, P〈0.001). The effect on the Der p 1 level was remarkably small (reduction factor: 1.2, P=0.48). In the intervention group, the Der f 1/Der p 1 ratio decreased after 12 months by a factor 2.0, whereas in the placebo group it increased (probability of the intervention effect: P〈0.005).Conclusion Mite-impermeable covers are more effective in reducing the level of Der f 1 than that of Der p 1.

Notes: Histamine-releasing factor or HRF is a collective term used for a heterogeneous group of factors with different modes of action. The current review is focussed on IgE-dependent HRF that require the presence of certain types of IgE (designated IgE+) to induce histamine release. IgE+ might be a structurally different IgE molecule, or, alternatively, autoreactive IgE. A subgroup of IgE-dependent HRF does not bind to IgE, such as cloned HRF p23. This factor turned out to be a basophil-priming cytokine. Alternatively IgE-dependent HRF might be an autoallergen. Several groups demonstrated IgE antibodies to human proteins. However, not all IgE autoallergen-containing extracts induce histamine release of appropriately sensitized basophils. In culture supernatants of human mononuclear cells an autoallergenic activity (Agmn) is found, but no binding to IgE+ was found yet. Agmn might be an autoallergen, since it is cross-reactive with a grass pollen allergen in the stripped basophil assay.IgE-dependent HRF and IgE+ may play a role in the late allergic reaction (LAR). However, IgE+ responsiveness to Agmn (IgEmn+) was not required for a bronchial LAR. IgEmn+ is associated with chronic allergic disease, since the prevalence of IgEmn+ is high in the serum of severe asthmatics and atopic dermatitis patients. Our hypothesis is that exogenous allergens induce IgE antibodies cross-reactive with an endogenous protein. During a LAR, these endogenous proteins are released and the subsequent IgE-mediated reaction prolongs and aggravates the allergic and/or asthmatic symptoms.In conclusion, HRF is a confusing term since it is used for different activities. It might be better to avoid this terminology on and just describe the activity of the factors. Autoallergenic activity is likely to explain most, if not all, IgE-dependent activity.

Notes: Background Reduction of allergen exposure from birth may reduce sensitization and subsequent allergic disease.Objective To measure the influence of mite allergen-impermeable mattress encasings and cotton placebo encasings on the amount of dust and mite allergen in beds.Methods A total of 810 children with allergic mothers took part in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study. Allergen-impermeable and placebo mattress encasings were applied to the childrens' and the parents' beds before birth. Dust samples were taken from the beds of children and their parents before birth and 3 and 12 months after birth. Extracts of dust samples were analysed for mite allergens (Der p 1 and Der f 1).Results Active mattress encasings were significantly more effective in reducing dust and mite allergen levels than placebo encasings. Mite allergen levels were low in general and the treatment effect was modest. Twelve months after birth, mattresses with active mattress encasings had about half the amount of Der 1 (Der p 1 + Der f 1)/m2, compared to mattresses with placebo encasings, for the child's and the parental mattress.Conclusion This study shows that mite-impermeable mattress encasings have a significant but modest effect on dust and mite allergen levels of mattresses with low initial mite allergen levels, compared to placebo.

Notes: Background It is presently unknown which factors determine the occurrence and persistence of asthma in house dust mite-allergic individuals. The level of allergen-specific IgE antibodies does not seem to be decisive for asthmatic symptoms. Moreover, levels of exposure to mite allergens do not seem to differ significantly between asthmatic and non-asthmatics individuals.Aim It was hypothesized that the presence or absence of asthmatic symptoms in house dust mite-allergic patients is associated with quantitative or qualitative differences in the cellular bronchial inflammatory response during the late phase of the allergic reaction. This hypothesis was tested in the bronchial allergen challenge model.Material and methods Whole lung challenges with house dust mite extract were performed in 52 house dust mite-allergic subjects, of whom 26 had asthma and 26 had perennial rhinitis without asthmatic symptoms. Primary outcomes were parameters for bronchial inflammation in serial samples of induced sputum (cell differentials, eosinophil cationic protein (ECP), interleukin-8 (IL-8), myeloperoxydase (MPO)). In addition, lung function, non-specific bronchial hyper- responsiveness and serial blood samples (eosinophils and IL-5) were analysed.Results At baseline sputum eosinophils and ECP were similar in both groups but neutrophils and IL-8 were higher in asthmatics. The early bronchoconstriction after allergen challenge was similar in asthma and non-asthmatic rhinitis (median decrease in FEV1: asthma − 31.7% vs. non-asthmatics − 29.1%, P 〉 0.1). The late phase bronchoconstriction was significantly greater in asthma (median decrease in FEV1: asthma − 27.6% vs. non-asthmatics − 18.9%, P = 0.02). Induction of bronchial hyper-responsiveness was similar in both groups. Bronchial allergen challenge elicited significant increases in sputum eosinophils and ECP, which were indistinguishable for both groups (P 〉 0.1 and P = 0.07, respectively). In contrast, higher numbers of neutrophils persisted in asthma 24 h after challenge and were accompanied by significant increases in IL-8 and MPO, which were absent in non-asthmatics (difference between groups P = 0.007 and P = 0.05, respectively).Conclusion Allergen challenge induced very similar increases in eosinophils and ECP in induced sputum in allergic asthmatics and in allergic non-asthmatic patients. The difference in bronchial inflammation between asthma and non-asthmatic rhinitis appeared to be more closely related to indices for neutrophilic inflammation.

Notes: Background It has been suggested that the period immediately after birth is a sensitive period for the development of atopic disease.Objective We investigated whether birth characteristics and environmental factors are associated with the development of atopic dermatitis in the first year of life.Methods Seventy-six children with and 228 without atopic dermatitis, all children of mothers with respiratory allergy or asthma (PIAMA birth cohort study) were included in the study. Atopic dermatitis was defined as a positive history of an itchy skin condition with at least two of the following characteristics: visible dermatitis, history of outer arms/leg involvement, or general dry skin. Multiple logistic regression analysis was performed to study the independent effects of various risk factors.Results A birth weight 〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:09547894:CEA1751:ges" location="ges.gif"/〉4000 g compared to 3000–4000 g was a significant risk factor for atopic dermatitis (odds ratio (OR)=2.4; 95% CI: 1.1–5.1) as was day care attendance (OR=2.9; 95% CI: 1.5–5.9). Exclusive breastfeeding in the first 3 months was negatively associated with atopic dermatitis (OR=0.6; 95% CI: 0.3–1.2), especially with visible dermatitis (OR=0.4; 95% CI: 0.2–1.0). Gender, gestational age, the presence of siblings or pets, and parental smoking were not significantly associated with atopic dermatitis.Conclusion This study shows that a high birth weight and day care attendance increase the risk of atopic dermatitis in the first year of life, while exclusive breastfeeding is a protective factor when dermatitis is found on inspection.

Notes: Background Sensitization to indoor allergens, particularly to dust mites, is a strong risk factor for asthma in children and adults. Assessment of sensitization is carried out using in vivo and in vitro tests to detect specific IgE antibodies.Objective To investigate IgE antibody responses to mites in patients with asthma, wheezing and/or rhinitis, using chimeric ELISA to measure specific IgE antibodies to mite allergens Der p 1 and Der p 2.Methods Specific IgE antibodies to Der p 1 and Der p 2 were quantified by chimeric ELISA, and compared with IgE to Dermatophagoides pteronyssinus (Dpt) measured using the CAP system (Pharmacia). A panel of sera from 212 patients with asthma, wheezing and/or rhinitis and 11 controls was analysed.Results There was a significant correlation between IgE to Dpt measured by CAP and IgE to Der p 1 (r = 0.81, P 〈 0.001), Der p 2 (r = 0.79, P 〈 0.001) and combined Der p 1 and Der p 2 (r = 0.86, P 〈 0.001). Seventy per cent of all patients had IgE to Dpt, and of those, 76.5% had IgE to Der p 1, 79.2% had IgE to Der p 2 and 83.1% had IgE to Der p 1 and Der p 2 combined. Considering the cut-off level of 2 IU/mL of IgE to either Der p 1 or Der p 2, the predictive value for a positive IgE to Dpt by CAP was greater than 95%.Conclusions The chimeric ELISA allowed accurate quantification of IgE antibodies to Dpt allergens Der p 1 and Der p 2, and it could be useful for studying immune responses to mites in patients with asthma and/or rhinitis.

Notes: Background The models for exposure to house dust in research and clinical practice are selected with respect to their role in IgE-mediated immediate hypersensitivity. The use of isolated major allergens instead of complex allergen extracts is becoming increasingly popular as it offers some important advantages for quantitative measures in diagnosis and research.Objective To compare house dust mite extract and isolated mite major allergens with respect to their ability to induce early and late asthmatic responses and bronchial hyperreactivity.Methods Bronchial responses to house dust mite (HDM, Dermatophagoides pteronyssinus) extract and isolated major allergens from HDM (Der p 1 and Der p 2) were compared in a double-blind, randomized, cross-over study in 20 patients with mild to moderate asthma who were allergic to HDM. Allergen was titrated to a standardized early asthmatic response. Bronchial hyper-responsiveness to histamine (PC20histamine) was determined before and after allergen inhalation to assess allergen-induced bronchial hyper-responsiveness and IL-5 was measured in serum. In addition, the allergens were applied in intracutaneous skin tests and activation of basophil leucocytes and proliferation of peripheral blood mononuclear cells was tested in vitro.Results After a similar early asthmatic response (mean Δforced expiratory volume in 1 s (FEV1),max−29.4 (SD 7.2) vs. −33.1 (8.6) %; mean difference 3.6 (95% CI −0.9 to 8.2) %), the late asthmatic response (mean ΔFEV1,max−45.9 (21.9) vs. −32.7 (22.3) %; mean difference 13.2 (3.8–22.3) %), the degree of allergen-induced bronchial hyper-responsiveness (mean ΔPC20histamine, 1.8 (1.0) vs. 1.2 (0.9) doubling dose; mean difference 0.6 (0.2–1.1) doubling dose) and serum IL-5 at 6 h were found to be significantly higher after bronchial challenge with HDM extract than after challenge with an isolated HDM major allergen. Likewise, there was an increased late skin reaction with HDM compared with isolated major allergen after a similar early skin reaction.Conclusion Constituents of HDM extract, other than Der p 1 or Der p 2, with no significant influence on the IgE-mediated early asthmatic response contribute significantly to the allergen-induced late asthmatic response and bronchial hyper-reactivity.