Molecular aspects of allergens in atopic dermatitis.
ABSTRACT: Molecular allergology uses pure, mainly recombinant and structurally defined allergen molecules and allergen-derived epitopes to study mechanisms of IgE-associated allergy, to diagnose, and even predict the development of allergic manifestations and to treat and prevent IgE-associated allergies. Atopic dermatitis, a chronic inflammatory skin disease is almost always associated with IgE sensitization to allergens. However, also non-IgE-mediated pathomechanisms seem to be operative in atopic dermatitis and it is often difficult to identify the disease-causing allergens. Here we review recent work showing the usefulness of molecular allergology to study mechanisms of atopic dermatitis, for diagnosis and eventually for treatment and prevention of atopic dermatitis.IgE sensitization to airborne, food-derived, microbial allergens, and autoallergens has been found to be associated with atopic dermatitis. Using defined allergen molecules and non-IgE-reactive allergen derivatives, evidence could be provided for the existence of IgE- and non-IgE-mediated mechanisms of inflammation in atopic dermatitis. Furthermore, effects of epicutaneous allergen administration on systemic allergen-specific immune responses have been studied. Multi-allergen tests containing micro-arrayed allergen molecules have been shown to be useful for the identification of culprit allergens in atopic dermatitis and may improve the management of atopic dermatitis by allergen-specific immunotherapy, allergen avoidance, and IgE-targeting therapies in a personalized medicine approach.Molecular allergology allows for dissection of the pathomechanisms of atopic dermatitis, provides new forms of allergy diagnosis for identification of disease-causing allergens, and opens the door to new forms of management by allergen-specific and T cells-targeting or IgE-targeting interventions in a personalized medicine approach.
Project description:<h4>Background</h4>The analysis of longitudinal birth cohorts with micro-arrayed allergen molecules has provided interesting information about the evolution of IgE sensitization in children. However, so far no cross-sectional study has been performed comparing IgE sensitization profiles in children with and without symptoms of allergy. Furthermore, no data are available regarding molecular IgE sensitization profiles in children from Russia.<h4>Methods</h4>We recruited two groups of age- and gender-matched children, one (Group 1: n = 103; 12.24 ± 2.23 years; male/female: 58/45) with symptoms and a second (Group 2: n = 97; 12.78 ± 2.23 years; male/female: 53/44), without symptoms of allergy according to international ISAAC questionnaire. Children were further studied regarding symptoms of allergy (rhinitis, asthma, atopic dermatitis) according to international guidelines, and skin prick testing with a panel of aeroallergen extracts was performed before sera were analyzed in an investigator-blinded manner for IgE specific to more than 160 micro-arrayed allergen molecules using ImmunoCAP ISAC technology.<h4>Results</h4>IgE sensitization = or >0.3 ISU to at least one of the micro-arrayed allergen molecules was found in 100% of the symptomatic children and in 36% of the asymptomatic children. Symptomatic and asymptomatic children showed a comparable IgE sensitization profile; however, frequencies of IgE sensitization and IgE levels to the individual allergen molecules were higher in the symptomatic children. Aeroallergen sensitization was dominated by sensitization to major birch pollen allergen, Bet v 1, and major cat allergen, Fel d 1. Food allergen sensitization was due to cross-sensitization to PR10 pollen and food allergens whereas genuine peanut sensitization was absent.<h4>Conclusion</h4>This is the first study analyzing molecular IgE sensitization profiles to more than 160 allergen molecules in children with and without symptoms of allergy. It detects similar molecular IgE sensitization profiles in symptomatic and asymptomatic children and identifies Bet v 1 and Fel d 1 as the predominant respiratory allergen molecules and PR10 proteins as the major food allergens and absence of genuine peanut allergy in Moscow region (Russia).
Project description:Allergen molecules (synonyms: single allergens, allergen components) open up new horizons for the targeted allergen-specific diagnostics of immunoglobulin E (IgE) in singleplex determination. The following rationales support the targeted use of allergen molecules and, more importantly, improve test properties: (1) increased test sensitivity ("analytical sensitivity"), particularly when important allergens are under-represented or lacking in the extract; (2) improved test selectivity (analytical specificity), particularly when the selected IgE repertoire against an allergen yields additional information on: (a) potential risk, (b) possible cross-reactivity, or (c) primary (species-specific) sensitization. However, the appropriate indication for the use of single allergens can only be established on a case-by-case basis (depending on the clinical context and previous history) and in an allergen-specific manner (depending on the allergen source and the single allergens available), rather than in a standardized way. Numerous investigations on suspected food allergy, insect venom allergy, or sensitization to respiratory allergens have meanwhile demonstrated the successful use of defined molecules for allergen-specific singleplex IgE diagnosis. Specific IgE to single allergens is limited in its suitability to predict the clinical relevance of sensitivity on an individual basis. In food allergies, one can at best identify the relative risk of a clinical reaction on the basis of an IgE profile, but no absolutely reliable prediction on (future) tolerance can be made. Ultimately, the clinical relevance of all IgE findings depends on the presence of corresponding symptoms and can only be assessed on an individual basis (previous history, symptom log, and provocation testing with the relevant allergen source where appropriate). Thus, also in molecular allergology, the treating physician and not the test result should determine the clinical relevance of diagnostic findings. ELECTRONIC SUPPLEMENTARY MATERIAL:Supplementary material is available for this article at 10.1007/s40629-015-0067-z and is accessible for authorized users.
Project description:<h4>Background</h4>In addition to allergen-specific IgE (sIgE), allergen-specific IgG4 (sIgG4) antibodies are also involved in the immune response resulting from an allergen exposure. The aim of our study was to analyze sIgE and sIgG4 patterns in the most common allergic disorders: bronchial asthma, upper airway disorders and atopic dermatitis.<h4>Methods</h4>In this study a screening analysis of blood serum samples from 673 patients aged from 6 months to 17 years with different allergic entities was performed on microarrays. sIgE and sIgG4 levels to the most common allergens were estimated.<h4>Results</h4>sIgE response to most pollen allergens is more strongly associated with respiratory diseases than with atopic dermatitis, while sIgE responses to cat and dog dander are more strongly associated with bronchial asthma than with atopic dermatitis and upper airway disorders such as rhinosinusitis and allergic rhinitis. A lower prevalence of sIgG4 to pollen allergens in cases of atopic dermatitis is observed compared with that in cases of asthma and upper airway disorders. Analyzing all the allergic disorders, one can see that sIgG4 response to inhalant allergens is strongly associated with sensitization to the corresponding allergen.<h4>Conclusion</h4>Allergen-specific IgE and IgG4 patterns that are relevant to concrete allergic diseases differ by sIgE and sIgG4 prevalences to defined allergens.
Project description:Measurement of IgE specific to purified house dust mite (HDM) allergens may improve allergy diagnosis. This study aimed to investigate the sensitization profiles of Korean HDM allergic subjects suffering from respiratory allergy and atopic dermatitis (AD) to Der f 1, Der f 2, Der f 6, Der f 8, Der f 10, and Der f 20.Recombinant HDM allergens were produced in Pichia pastoris (Der f 1) or Escherichia coli (5 allergens). IgE reactivity to the individual recombinant allergens and total extract of mite was assessed by ELISA.Der f 1 was recognized by 79.1%, Der f 2 by 79.1%, Der f 6 by 9.3%, Der f 8 by 6.2%, Der f 10 by 6.2%, and Der f 20 by 6.6% of the patients' sera tested, while the prevalence of IgE reactivity to total mite extract was 94.7%. Combination of Der f 1 and Der f 2 had a sensitivity of 87.6%. Specific IgE to Der f 2 alone was detected from 89.4% of HDM-sensitized respiratory allergy subjects and 92.3% to the combination of the 2 major allergens Der f 1 and Der f 2. However, sera from fewer patients with AD, namely 72.4% and 71.0%, recognized Der f 1 and Der f 2, respectively. The combination of 2 major allergens allowed diagnosis of 84.5% of the AD patients. No correlation between sensitization to specific allergens and HDM allergy entity was found.Der f 2 was the most frequently sensitized allergen among the HDM-sensitized respiratory and AD patients in Korea, and the combination of the group 1 and 2 major allergens increased the diagnostic sensitivity. Minor allergens did not significantly improve diagnostic sensitivity. However, further studies are needed to analyze the relationship between sensitization to other HDM allergens and the disease entity of the HDM allergy.
Project description:Atopic dermatitis can be due to a variety of causes from nonatopic triggers to food allergy. Control of egress of water and protection from ingress of irritants and allergens are key components of cutaneous barrier function. Current research suggests that a degraded barrier function of the skin allows the immune system inappropriate access to environmental allergens. Epidermal aeroallergen exposure may allow sensitization to allergen possibly initiating the atopic march. Further research into connections between epidermal barrier function and possible allergen sensitization will be important to undertake. Future clinical trials focused on skin barrier protection may be of value as a possible intervention in prevention of the initiation of the atopic march.
Project description:BACKGROUND:Maternal diet during pregnancy may affect childhood allergy and asthma. OBJECTIVE:We sought to examine the associations between maternal intake of common childhood food allergens during early pregnancy and childhood allergy and asthma. METHODS:We studied 1277 mother-child pairs from a US prebirth cohort unselected for any disease. Using food frequency questionnaires administered during the first and second trimesters, we assessed maternal intake of common childhood food allergens during pregnancy. In mid-childhood (mean age, 7.9 years), we assessed food allergy, asthma, allergic rhinitis, and atopic dermatitis by questionnaire and serum-specific IgE levels. We examined the associations between maternal diet during pregnancy and childhood allergy and asthma. We also examined the cross-sectional associations between specific food allergies, asthma, and atopic conditions in mid-childhood. RESULTS:Food allergy was common (5.6%) in mid-childhood, as was sensitization to at least 1 food allergen (28.0%). Higher maternal peanut intake (each additional z score) during the first trimester was associated with 47% reduced odds of peanut allergic reaction (odds ratio [OR], 0.53; 95% CI, 0.30-0.94). Higher milk intake during the first trimester was associated with reduced asthma (OR, 0.83; 95% CI, 0.69-0.99) and allergic rhinitis (OR, 0.85; 95% CI, 0.74-0.97). Higher maternal wheat intake during the second trimester was associated with reduced atopic dermatitis (OR, 0.64; 95% CI, 0.46-0.90). Peanut, wheat, and soy allergy were each cross-sectionally associated with increased childhood asthma, atopic dermatitis, and allergic rhinitis (ORs, 3.6 to 8.1). CONCLUSION:Higher maternal intake of peanut, milk, and wheat during early pregnancy was associated with reduced odds of mid-childhood allergy and asthma.
Project description:Background:Rhinitis is a common problem within the population. Many subjects with rhinitis also have atopic multimorbidity, such as asthma and eczema. The purpose of this investigation was to compare subjects with only rhinitis to those that have rhinitis, asthma and/or eczema in relation to immunoglobulin E (IgE) sensitization, inflammatory markers, family history, lung function and body mass index (BMI). Methods:A total of 216 adult subjects with rhinitis from the European Community Respiratory Health Survey II were investigated with multiplex component allergen analysis (103 allergen components), total IgE, C-reactive protein, eosinophilic cationic protein, fractional exhaled nitric oxide and spirometry. Rhinitis, eczema, asthma and parental allergy were questionnaire-assessed. Results:Of the 216 participants with rhinitis, 89 also had asthma and/or eczema. Participants with rhinitis that also had asthma or eczema were more likely to be IgE-sensitized (3.44, odds ratio, OR: 95% CI 1.62-7.30, adjusted for sex, age, mother's allergy, total IgE and forced expiratory volume (FEV1)). The number of IgE-positive components was independently associated with atopic multimorbidity (1.11, OR: 95% Cl 1.01-1.21) adjusted for sex, age, mother's allergy, total IgE and FEV1. When analysing different types of sensitization, the strongest association with atopic multimorbidity was found in participants that were IgE-sensitized both to perennial and seasonal allergens (4.50, OR: 95% CI 1.61-12.5). Maternal allergy (2.75, OR: 95% CI 1.15-4.46), high total IgE (2.38, OR: 95% CI 1.21-4.67) and lower FEV1 (0.73, OR: 95% CI 0.58-0.93) were also independently associated with atopic multimorbidity, while no association was found with any of the other inflammatory markers. Conclusion:IgE polysensitization, to perennial and seasonal allergens, and levels of total IgE seem to be the main determinants of atopic multimorbidity in subjects with rhinitis. This indicates that disease-modifying treatment that targets IgE sensitization may be of value when decreasing the risk of developing atopic multimorbidity.
Project description:Molecular allergy is based on identification, characterization and subsequent use of single allergens, being components of complex allergen sources like pollen, mites, furred animals, foods or insect venoms. Only few protein families contain relevant allergens of similar sequence and structure, carrying common IgE epitopes as the basis of cross reactivity. Used as purified or recombinant (glyco)proteins single allergens can potentially improve in-vitro diagnostics, particularly allergen-specific IgE assays through a) increased sensitivity, b) use of risk and marker allergens, c) component-resolved diagnostics (CRD). CRD can differentiate primary, species-specific from secondary, cross-reactive sensitizations to single allergens. Allergen components facilitate an increased analytical sensitivity, particularly if they are underrepresented or missing in conventional allergen extracts. They are mainly used in single assays (singleplex) for the detection of IgE, but also in a microarray format (multiplex) with 112 components from 50 allergen sources with slightly decreased analytical sensitivity. Concepts of molecular allergy can only be separately defined and utilized for each allergen source (pollen, mites, foods or insect venoms). As soon as essential singe allergens are available, their specific role in diagnostics should be defined. This requires well characterized patient cohorts from various countries, since exposure, allergic immune response and clinical relevance can vary substantially between individual subjects and geographical regions. The patient's clinical information is essential for proper interpretation of molecular allergology results. The history and/or challenge test results will finally provide evidence, in how far a sensitization to single allergens might be clinically relevant or not.
Project description:BACKGROUND:Atopic dermatitis (AD) is a complex chronic inflammatory disease where allergens can act as specific triggering factors. AIM:To characterize the specificities of IgE-reactivity in patients with AD to a broad panel of exogenous allergens including microbial and human antigens. METHODOLOGY:Adult patients with AD were grouped according to the SCORAD index, into severe (n = 53) and moderate AD (n = 126). As controls 43 patients were included with seborrhoeic eczema and 97 individuals without history of allergy or skin diseases. Specific IgE reactivity was assessed in plasma using Phadiatop®, ImmunoCap™, micro-arrayed allergens, dot-blotted recombinant Malassezia sympodialis allergens, and immune-blotted microbial and human proteins. RESULTS:IgE reactivity was detected in 92% of patients with severe and 83% of patients with moderate AD. Sensitization to cat allergens occurred most frequently, followed by sensitization to birch pollen, grass pollen, and to the skin commensal yeast M. sympodialis. Patients with severe AD showed a significantly higher frequency of IgE reactivity to allergens like cat (rFel d 1) and house dust mite (rDer p 4 and 10), to Staphylococcus aureus, M. sympodialis, and to human antigens. In contrast, there were no significant differences in the frequencies of IgE reactivity to the grass pollen allergens rPhl p 1, 2, 5b, and 6 between the two AD groups. Furthermore the IgE reactivity profile of patients with severe AD was more spread towards several different allergen molecules as compared to patients with moderate AD. CONCLUSION:We have revealed a hitherto unknown difference regarding the molecular sensitization profile in patients with severe and moderate AD. Molecular profiling towards allergen components may provide a basis for future investigations aiming to explore the environmental, genetic and epigenetic factors which could be responsible for the different appearance and severity of disease phenotypes in AD.
Project description:BACKGROUND: Limited data are available on the frequency of IgE mediated food sensitization and food allergy (FA) in adults with atopic dermatitis (AD). OBJECTIVE: We investigated the pattern of food sensitization in adults with AD in relation to AD severity using multiplexed allergen microarray. METHODS: 211 adult patients referred between January 2010-July 2011 for evaluation of AD were unselectively included. Severity of AD was determined by therapy intensity, SASSAD-skin-score and sTARC levels. Allergen specific sIgE levels were measured by ImmunoCAP ISAC® microarray. FA was defined as convincing history taken by physician and sensitization to the corresponding allergen. RESULTS: Sensitization to food was found in 74.4% of the AD patients, 54% had a positive history of FA and 20.4% asymptomatic sensitization. There was no association between severity of AD and frequency of food sensitization or history of FA.Sensitization to PR-10 related food allergens occurred most frequently (63.5%) and was independent from AD severity. Correspondingly, pollen-food syndrome accounted for most of the FA, being also independent from AD severity. Of all plant food allergens only sensitization to nAra h 1 was significantly more frequent in patients with severe AD. In the total group 75 (35.5%) patients with AD showed sensitization to any animal food allergen. The percentage was significantly higher in patients with severe AD (51.4%) compared to patients with mild/moderate AD (27.7%). Sensitization to cow's milk allergens, in particular to nBos d lactoferrin, was more frequent in severe AD patients. CONCLUSION: AD was frequently associated with food sensitization. The percentage of sensitization to animal food allergens was significantly higher in severe AD patients.