| 1. |
- Calderon, Moises A, et al.
(författare)
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EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy.
- 2012
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy.Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies.Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals' quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases.Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in which Europe is recognized as a worldwide leader. Evaluation and surveillance of the full cost of allergic diseases is still lacking and further progress is being stifled by the variety of health systems across Europe. This means that the general population remains unaware of the potential use of allergen specific immunotherapy and its potential benefits.We call upon Europe's policy-makers to coordinate actions and improve individual and public health in allergy by:Promoting awareness of the effectiveness of allergen specific immunotherapyUpdating national healthcare policies to support allergen specific immunotherapyPrioritising funding for allergen specific immunotherapy researchMonitoring the macroeconomic and health economic parameters of allergyReinforcing allergy teaching in medical disciplines and specialtiesThe effective implementation of the above policies has the potential for a major positive impact on European health and well-being in the next decade.
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| 2. |
- Moverare, Robert, et al.
(författare)
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Evaluation of IgE Antibodies to Recombinant Peanut Allergens in Patients with Reported Reactions to Peanut
- 2011
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 156:3, s. 282-290
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Tidskriftsartikel (refereegranskat)abstract
- Background: Peanut may cause severe reactions in allergic individuals. The objective was to evaluate IgE antibodies to various recombinant (r) peanut and birch pollen allergens in relation to IgE levels to whole peanut extract and severe allergic reactions to peanut. Methods: Seventy-four Swedish peanut-allergic patients (age: 14-61 years) reported previous peanut exposure and associated symptoms using a questionnaire. Their IgE reactivity to peanut, birch pollen and individual allergen components was analyzed using ImmunoCAP(R). Results: Of the 48 subjects sensitized to Ara h 1, 2 or 3, 60% had peanut-specific IgE levels >15 kU(A)/l, while 100% of the subjects without detectable IgE to these allergens had low peanut-specific IgE levels (<10 kU(A)/l). The levels of IgE to rAra h 8, rBet v 1 and birch pollen were highly correlated (r(S) = 0.94, p < 0.0001). Fifty-eight patients reported adverse reactions after accidental or deliberate peanut exposure (oral, inhalation or skin) of whom 41 had IgE to rAra h 1, 2 or 3. Symptoms of respiratory distress were associated with sensitization to Ara h 1, 2 or 3 (56 vs. 18%, p < 0.01). Two cases of anaphylaxis were reported among the individuals sensitized to Ara h 1-3. IgE to rAra h 8, rAra h 9, profilin or cross-reactive carbohydrate determinants were not associated with severe symptoms. Conclusions: The results indicate that IgE reactivity to Ara h 1, 2 and 3 is associated with severe reactions after exposure to peanut in Swedish patients.
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| 3. |
- Arkestål, Kurt, et al.
(författare)
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Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-alpha 1,3-galactose
- 2011
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 127:4, s. 1024-1028
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Tidskriftsartikel (refereegranskat)abstract
- Background: The carbohydrate epitope galactose-alpha 1,3galactose (a-Gal) is abundantly expressed on nonprimate mammalian proteins. We have recently shown that alpha-Gal is responsible for the IgE binding to cat IgA, a newly identified cat allergen (Fel d 5). Objective: We sought to investigate the diagnostic relevance of IgE antibodies to Fel d 5 and a-Gal among parasite-infected patients from central Africa without cat allergy compared with patients with cat allergy from the same region. Methods: Sera from 47 parasite-infected patients and 31 patients with cat allergy were analyzed for total IgE and IgE antibodies against cat dander extract (CDE) by using the ImmunoCAP system. Inhibition assay was performed with a-Gal on solid phase-bound CDE. The presence of IgE specific for the major cat allergen Fel d 1, Fel d 5, and alpha-Gal was analyzed by means of ELISA. Results: Among the 47 parasite-infected patients, 85% had IgE antibodies against alpha-Gal (OD; median, 0.175; range, 0.1021.466) and 66% against Fel d 5 (OD; median, 0.13; range, 0.1031.285). Twenty-four of the parasite-infected patients were sensitized to CDE, and 21 of them had IgE antibodies to Fel d 5 and a-Gal. There was no correlation between IgE levels to CDE and rFel d 1 among the parasite-infected patients but a strong correlation between CDE and Fel d 5 and alpha-Gal (P <. 001). Among the group with cat allergy, only 5 patients had IgE to alpha-Gal, and nearly 75% (n 5 23) had IgE to rFel d 1 (median, 7.07 kU(A)/L; range, 0.51-148.5 kUA/ L). In contrast, among the patients with cat allergy, there was a correlation between IgE levels to CDE and rFel d 1 (P <.05) but no correlation between CDE and Fel d 5 and alpha-Gal. Conclusion: IgE to alpha-Gal causes impaired allergy diagnostics in parasite-infected patients. Screening for IgE to rFel d 1 and other allergens without carbohydrates might identify patients with true cat sensitization/ allergy in parasite-infested areas.
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| 4. |
- Bornelöv, Susanne, et al.
(författare)
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Rule-Based Models of the Interplay between Genetic and Environmental Factors in Childhood Allergy
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. e80080-
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Tidskriftsartikel (refereegranskat)abstract
- Both genetic and environmental factors are important for the development of allergic diseases. However, a detailed understanding of how such factors act together is lacking. To elucidate the interplay between genetic and environmental factors in allergic diseases, we used a novel bioinformatics approach that combines feature selection and machine learning. In two materials, PARSIFAL (a European cross-sectional study of 3113 children) and BAMSE (a Swedish birth-cohort including 2033 children), genetic variants as well as environmental and lifestyle factors were evaluated for their contribution to allergic phenotypes. Monte Carlo feature selection and rule based models were used to identify and rank rules describing how combinations of genetic and environmental factors affect the risk of allergic diseases. Novel interactions between genes were suggested and replicated, such as between ORMDL3 and RORA, where certain genotype combinations gave odds ratios for current asthma of 2.1 (95% CI 1.2-3.6) and 3.2 (95% CI 2.0-5.0) in the BAMSE and PARSIFAL children, respectively. Several combinations of environmental factors appeared to be important for the development of allergic disease in children. For example, use of baby formula and antibiotics early in life was associated with an odds ratio of 7.4 (95% CI 4.5-12.0) of developing asthma. Furthermore, genetic variants together with environmental factors seemed to play a role for allergic diseases, such as the use of antibiotics early in life and COL29A1 variants for asthma, and farm living and NPSR1 variants for allergic eczema. Overall, combinations of environmental and life style factors appeared more frequently in the models than combinations solely involving genes. In conclusion, a new bioinformatics approach is described for analyzing complex data, including extensive genetic and environmental information. Interactions identified with this approach could provide useful hints for further in-depth studies of etiological mechanisms and may also strengthen the basis for risk assessment and prevention.
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| 5. |
- Lundstrom, Susanna L., et al.
(författare)
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Allergic Asthmatics Show Divergent Lipid Mediator Profiles from Healthy Controls Both at Baseline and following Birch Pollen Provocation
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a respiratory tract disorder characterized by airway hyper-reactivity and chronic inflammation. Allergic asthma is associated with the production of allergen-specific IgE and expansion of allergen-specific T-cell populations. Progression of allergic inflammation is driven by T-helper type 2 (Th2) mediators and is associated with alterations in the levels of lipid mediators. Objectives: Responses of the respiratory system to birch allergen provocation in allergic asthmatics were investigated. Eicosanoids and other oxylipins were quantified in the bronchoalveolar lumen to provide a measure of shifts in lipid mediators associated with allergen challenge in allergic asthmatics. Methods: Eighty-seven lipid mediators representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened via LC-MS/MS following off-line extraction of bronchoalveolar lavage fluid (BALF). Multivariate statistics using OPLS were employed to interrogate acquired oxylipin data in combination with immunological markers. Results: Thirty-two oxylipins were quantified, with baseline asthmatics possessing a different oxylipin profile relative to healthy individuals that became more distinct following allergen provocation. The most prominent differences included 15-LOX-derived omega-3 and omega-6 oxylipins. Shared-and-Unique-Structures (SUS)-plot modeling showed a correlation (R-2 = 0.7) between OPLS models for baseline asthmatics ((RY)-Y-2[cum] = 0.87, Q(2)[cum] = 0.51) and allergen-provoked asthmatics ((RY)-Y-2[cum] = 0.95, Q(2)[cum] = 0.73), with the majority of quantified lipid mediators and cytokines contributing equally to both groups. Unique structures for allergen provocation included leukotrienes (LTB4 and 6-trans-LTB4), CYP-derivatives of linoleic acid (epoxides/diols), and IL-10. Conclusions: Differences in asthmatic relative to healthy profiles suggest a role for 15-LOX products of both omega-6 and omega-3 origin in allergic inflammation. Prominent differences at baseline levels indicate that non-symptomatic asthmatics are subject to an underlying inflammatory condition not observed with other traditional mediators. Results suggest that oxylipin profiling may provide a sensitive means of characterizing low-level inflammation and that even individuals with mild disease display distinct phenotypic profiles, which may have clinical ramifications for disease.
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| 6. |
- Nilsson, Ola B., et al.
(författare)
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Designing a Multimer Allergen for Diagnosis and Immunotherapy of Dog Allergic Patients
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dog dander extract used for diagnosis and allergen-specific immunotherapy is often of variable and of poor quality.Objective: To assemble four well-established dog allergen components into one recombinant folded protein for improved diagnosis and vaccination of allergy to dog.Methods: A linked molecule, comprising the four dog lipocalin allergens Can f 1, Can f 2, Can f 4 and Can f 6 was constructed. The tetrameric protein was structurally characterized by small angle X-ray scattering, and compared with each single recombinant lipocalin allergen or an equimolar mix of the four allergens by analytical size exclusion chromatography, circular dichroism, allergen-specific IgE in serum by ELISA and allergen-dependent capacity to activate basophils. The immunogenicity of the fusion protein was evaluated in immunized mice by assessing splenocyte proliferation and antibody production.Results: The linked tetrameric construct was produced as a soluble fusion protein, with the specific folds of the four individual allergens conserved. This multi-allergen molecule was significantly more efficient (p < 0.001) than each single recombinant allergen in binding to dog-specific IgE, and the epitope spectrum was unaffected compared to an equimolar mix of the four allergens. Basophil degranulation revealed that the biologic activity of the linked molecule was retained. Immunization of mice with the linked construct induced comparable allergen-specific IgG responses with blocking capacity towards all included allergens and generated comparably low T-cell responses.Conclusion: We provide the first evidence for a linked recombinant molecule covering the major dog allergens for potential use in diagnostics and allergy vaccination of dog allergic patients.
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| 7. |
- Nilsson, Ola B., et al.
(författare)
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Mammalian-derived respiratory allergens - Implications for diagnosis and therapy of individuals allergic to furry animals
- 2014
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Ingår i: Methods. - : Elsevier BV. - 1046-2023 .- 1095-9130. ; 66:1, s. 86-95
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Tidskriftsartikel (refereegranskat)abstract
- Furry animals cause respiratory allergies in a significant proportion of the population. A majority of all mammalian allergens are spread as airborne particles, and several have been detected in environments where furry animals are not normally kept. The repertoire of allergens from each source belongs to a restricted number of allergen families. Classification of allergen families is particularly important for the characterization of allergenicity and cross-reactivity of allergens. In fact, major mammalian allergens are taken from only three protein families, i.e. the secretoglobin, lipocalin and kallikrein families. In particular, the lipocalin superfamily harbours major allergens in all important mammalian allergen sources, and cross-reactivity between lipocalin allergens may explain cross-species sensitization between mammals. The identification of single allergen components is of importance to improve diagnosis and therapy of allergic patients using component-resolved diagnostics and allergen-specific immunotherapy (ASIT) respectively. Major disadvantages with crude allergen extracts for these applications emphasize the benefits of careful characterization of individual allergens. Furthermore, detailed knowledge of the characteristics of an allergen is crucial to formulate attenuated allergy vaccines, e.g. hypoallergens. The diverse repertoires of individual allergens from different mammalian species influence the diagnostic potential and clinical efficacy of ASIT to furry animals. As such, detailed knowledge of individual allergens is essential for adequate clinical evaluation. This review compiles current knowledge of the allergen families of mammalian species, and discusses how this information may be used for improved diagnosis and therapy of individuals allergic to mammals.
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