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Sökning: WFRF:(van Hage Marianne)

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1.
  • Calderon, Moises A, et al. (författare)
  • EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy.
  • 2012
  • Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
  • 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)
  • Evaluation of IgE Antibodies to Recombinant Peanut Allergens in Patients with Reported Reactions to Peanut
  • 2011
  • Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 156:3, s. 282-290
  • 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.
  • Almqvist, Catarina, et al. (författare)
  • Heredity, pet ownership, and confounding control in a population-based birth cohort
  • 2003
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 111, s. 800-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The association between pet ownership in childhood and subsequent allergic disease is controversial. Bias related to selection of pet exposure has been suggested as a reason for contradictory study results.OBJECTIVE: The purpose of this investigation was to elucidate how pet exposure depends on family history of allergic disease, smoking, and socioeconomic factors in a prospective birth cohort.METHODS: Parents of 4089 two-month-old children answered a questionnaire that included detailed questions about family history of asthma (maternal, paternal, and sibling), rhinoconjunctivitis, atopic eczema/dermatitis syndrome, pollen and pet allergy, smoking habits, parental occupation, and family pet ownership (cat and dog). Dust samples collected from the mothers' beds were analyzed for Fel d 1 and Can f 1 in a subgroup of the cohort.RESULTS: Cats were less frequently kept in families with parental asthma, rhinoconjunctivitis, or pet or pollen allergy (3.5% to 5.8%) than in families without parental allergic disease (10.8% to 11.8%). Dogs were less common in families with (3.3%) than in families without (5.9%) parental atopic eczema/dermatitis syndrome. Families with smoking mothers and those with low socioeconomic index kept cats and dogs more frequently. Cat allergen levels were lower in homes with than in homes without maternal pet allergy, and this tended to hold true even for homes without a cat. Cat ownership decreased from birth to 2 years of age, especially in families with parental history of allergic diseases.CONCLUSION: There seems to be a selection of pet exposure based on parental history of allergy, maternal smoking, and socioeconomic factors. This has to be taken into consideration in evaluations of risk associations between pet exposure and allergic disease in childhood.
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4.
  • Arkestål, Kurt, et al. (författare)
  • Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-alpha 1,3-galactose
  • 2011
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 127:4, s. 1024-1028
  • 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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5.
  • Bager, Jessica, et al. (författare)
  • Prevalence and early-life risk factors for tree nut sensitization and allergy in young adults
  • 2021
  • Ingår i: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 51:11, s. 1429-1437
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Tree nut allergy may cause anaphylaxis. There are limited population-based studies on prevalence and early-life risk factors. Methods We evaluated the prevalence of reported symptoms and allergic sensitization to tree nuts at age 24 years in the BAMSE population-based cohort study and assessed early-life factors associated with the development of tree nut allergy. We estimated tree nut allergy prevalence, by analysing questionnaire data on tree nut ingestion and symptoms at age 12, 16 and 24 years, and IgE sensitization at age 24 years to hazelnut, walnut, pecan, cashew, pistachio, Brazil nut, almond extracts and allergen molecules Cor a 1, 9, 14 (hazelnut), Jug r 1 (walnut) and Ana o 3 (cashew). We evaluated eczema, asthma, food allergies, inherited risk of allergy and gender as potential early-life risk factors. Results Data were available for 2215/4089 (54%) BAMSE study participants, for estimation of the prevalence of tree nut sensitization (21.2%), tree nut allergy symptoms (9.8%) and combined sensitization and symptoms (7.9%, 2.1% for storage protein sensitization and symptoms, 4.3% for any sensitization and non-mild symptoms). Sixty-three per cent of sensitized individuals (295/470) were asymptomatic, but only 76/470 (16%) storage protein sensitized individuals. Egg allergy (ORadj 8.50 95% CI 2.15-33.6), eczema (ORadj 2.53 95% CI 1.21-5.32) and asthma (ORadj 5.59 95% CI 2.35-13.3)) at pre-school age were associated with future development of tree nut symptoms and storage protein sensitization. At age 24 years, tree nut allergy was associated with current eczema and with markers of current asthma severity. Sensitization to storage proteins was more strongly associated with symptoms than sensitization to whole extract for all tree nuts evaluated. Conclusions In this Swedish cohort, we found tree nut whole extract sensitization is common but usually asymptomatic. Storage protein sensitization is a more reliable indicator of tree nut symptoms. Tree nut allergy is associated with early onset, persistent and severe atopic disease.
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6.
  • Bornelöv, Susanne, et al. (författare)
  • Rule-Based Models of the Interplay between Genetic and Environmental Factors in Childhood Allergy
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. e80080-
  • 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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7.
  • Ferrándiz, Rafael, 1953- (författare)
  • Allergenic characterization of the domestic mite Dermatophagoides siboney
  • 1997
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Allergic reactions to Pyroglyphid mites of the genus Dennatophagoides play an important role in the pathogenesis of asthma and other atopic diseases. Dermatophagoides siboney was described in Cuba in 1982. D. pteronyssinus and D. siboney are the most frequent mites in house dust collected from the homes of Cuban asthmatics, i.e., 100 and 85%, respectively.The aims of the present studies were to investigate the prevalence of sensitization to D. siboney, Blomia tropicalis and other mite species in asthmatic patients from Cuba; to study the allergenic composition and to characterize the major allergens of D. siboney extracts; to investigate the crossreactivity between D. siboney and other mite allergens, and the relevance of patient selection for the determination of the biological activity of D. siboney and other domestic mites in the tropics.Dermatophagoides siboney was found to be an important sensitizing agent among asthmatics in Cuba. Sensitization to B. tropicalis, D. pteronyssinus, D. farinae and A. siro, was also common as studied by skin and specific IgE tests. A combination of SPT with D. siboney, D. pteronyssinus and B. tropicalis diagnosed sensitization to mites in almost all mite sensitive patients. Thirteen allergenic proteins were identified in D. siboney extracts. Three components, 25, 14 and 30 kD, which bound to specific IgE strongly and frequently, were purified by affinity chromatography using crossreacting monoclonal antibodies to group 1; 2 and 3 allergens and named Der s 1, Der s 2 and Der s 3, respectively. TheN-terminal sequences of these allergens showed higher homology with D. jarinae and D. microceras than with D. pteronyssinus. The homology between group 2 allergens was higher than that of group 1 and 3 allergens.A higher degree of crossreactivity was observed between allergens from D. siboney and D. farinae than betWeen D. siboney and D. pteronyssinus, B. tropicalis, A. siro, L. destructor or T. putrescentiae. Due to the crossreactivity, Cubans not exposed to D. farinae and Swedes not exposed to D. siboney and B. tropicalis, reacted to these mites. The individual allergens of D. siboney crossreacted more with those of D. farinae and D. microceras than with those of D. pteronyssinus. The 65, 62, 37 and 30 kD proteins, always inhibited by more than 50 % by the other mite species, were the main cause of the crossreactivity, The 80 kD protein was the less crossreactive allergen. Three MoAbs directed to Der s 1, one group crossreacting and two species specific, were produced. The crossreacting monoclonal antibody partly inhibited IgE binding to Der s 1 allergen. The results confmned the existence of crossreacting epitopes onDer s 1 but also indicate that this allergen has at least one species specific epitope.The degree of reactivity to different mites seemed to be more related to patient selection criteria and extract potency rather than to exposure to a specific species.Since D. siboney is common in dust from Cuban homes, it is probably present in other Caribbean countries and found to be an important sensitizer, it has been considered a potential candidate for the development of extracts for diagnosis and therapy of mite allergy. These studies contribute to the understanding of the characteristics of the allergens from this species and their relation to other mite allergens.
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8.
  • Hjortswang, Henrik, et al. (författare)
  • Infliximab in clinical routine : Experience with Crohn's disease and biomarkers of inflammation over 5 years
  • 2009
  • Ingår i: European Journal of Gastroenterology and Hepathology. - 0954-691X .- 1473-5687. ; 21:10, s. 1168-1176
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Infliximab was launched for the treatment of Crohn's disease (CD) in 1999. We set up a follow-up protocol to meticulously study disease development with repeated infusions of infliximab.  Aim: To follow the effects of infliximab treatment on disease activity, blood chemistry, quality of life, plasma nitrite, and titers of Saccharomyces cerevisiae antibodies (ASCA). Methods: During 1999–2008, CD patients were monitored for disease activity by Harvey–Bradshaw index, blood chemistry with hemoglobin, albumin, C-reactive protein, platelet count, leukocyte count and creatinine, quality of life by the Short Health Scale, and plasma nitrite. During the first year of treatment, follow-up was done repeatedly before and 1 week after each infusion and thereafter every year before the last infusion for 5 years. ASCA was analyzed by flow cytometry with fluorescein isothiocyanate-labelled antibodies. Results: A total of 1061 infusions were given to 103 patients; 92 responders and 11 nonresponders. Responders were further monitored and Harvey–Bradshaw index decreased with infusions during the first year of treatment (P<0.0001), whereas hemoglobin (P<0.01) and albumin (P<0.001) increased, C-reactive protein (P<0.01) decreased, platelets (P<0.001) increased, and leukocytes (P<0.01) decreased. Creatinine was not affected. Short Health Scale (questions analyzed separately) decreased (P<0.0001), and nitrite (P<0.001) increased. During the next 4 years the improved values remained stable. Adverse effects were noted among 32% of the patients; local circulatory reactions being most common. No correlation between ASCA titers and inflammatory activity or infliximab treatment was found. Conclusion: Infliximab treatment is highly effective in responders and maintains symptomatic improvement and low inflammatory activity over years in CD patients.
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9.
  • Holmdahl, Idun, et al. (författare)
  • Early Life Wheeze and Risk Factors for Asthma-A Revisit at Age 7 in the GEWAC-Cohort
  • 2021
  • Ingår i: Children. - : MDPI. - 2227-9067. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • One third of all toddlers are in need of medical care because of acute wheeze and many of these children have persistent asthma at school age. Our aims were to assess risk factors for and the prevalence of asthma at age 7 in a cohort of children suffering from an acute wheezing episode as toddlers. A total of 113 children, included during an acute wheezing episode (cases), and 54 healthy controls were followed prospectively from early pre-school age to 7 years. The protocol included questionnaires, ACT, FeNO, nasopharyngeal virus samples, blood sampling for cell count, vitamin D levels, and IgE to food and airborne allergens. The prevalence of asthma at age 7 was 70.8% among cases and 1.9% among controls (p < 0.001). Acute wheeze caused by rhinovirus (RV) infection at inclusion was more common among cases with asthma at age 7 compared to cases without asthma (p = 0.011) and this association remained significant following adjustment for infection with other viruses (OR 3.8, 95% CI 1.4-10.5). Cases with asthma at age 7 had been admitted to hospital more often (p = 0.024) and spent more days admitted (p = 0.01) during the year following inclusion compared to cases without asthma. RV infection stands out as the main associated factor for wheeze evolving to persistent asthma. Cases who developed asthma also had an increased need of hospital time and care for wheeze during the year after inclusion.
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10.
  • Holmdahl, Idun, et al. (författare)
  • Inflammatory related plasma proteins involved in acute preschool wheeze
  • 2023
  • Ingår i: Clinical and Translational Allergy. - : John Wiley & Sons. - 2045-7022. ; 13:11
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPreschool wheeze is a risk factor for asthma development. However, the molecular mechanism behind a wheezing episode is not well understood.ObjectiveOur aims were to assess the association of plasma proteins with acute preschool wheeze and to study the proteins with differential expression at the acute phase at revisit after 3 months. Additionally, to investigate the relationship between protein expression and clinical parameters.MethodWe measured 92 inflammatory proteins in plasma and clinical parameters from 145 children during an episode of preschool wheeze (PW) and at the revisit after 3 months (PW-R, n = 113/145) and 101 healthy controls (HC) aged 6–48 months in the GEWAC cohort using the antibody-mediated proximity extension-based assay (Olink Proteomics, Uppsala).ResultsOf the 74 analysed proteins, 52 were differentially expressed between PW and HC. The expression profiles of the top 10 proteins, Oncostatin M (OSM), IL-10, IL-6, Fibroblast growth factor 21 (FGF21), AXIN1, CXCL10, SIRT2, TNFSF11, Tumour necrosis factor β (TNF-β) and CASP8, could almost entirely separate PW from HC. Five out of 10 proteins were associated with intake of oral corticosteroids (OCS) 24 h preceding blood sampling (OSM, CASP8, IL-10, TNF-β and CXCL10). No differences in protein expression were seen between PWs with or without OCS in comparison to HC. At the revisit after 3 months, differential protein expressions were still seen between PW-R and HC for three (IL-10, SIRT2 and FGF21) of the 10 proteins.ConclusionOur results contribute to unravelling potential immunopathological pathways shared between preschool wheeze and asthma.
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11.
  • Holmström, Mats, et al. (författare)
  • Nasal complaints and signs of disease in farmers : a methodological study
  • 2008
  • Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 128:2, s. 193-200
  • Tidskriftsartikel (refereegranskat)abstract
    • CONCLUSION: The methods used in this study are suitable for field studies that involve examinations of groups of workers. For individual examinations, there is no gold standard method that can discriminate work-related discomfort from other causes of rhinitis. OBJECTIVES: Studies of the effects of occupation on farmers' health have mainly focused on lower airways; few studies have examined effects on upper airways. This study investigated nasal functions in three groups of farmers (swine, milk and grain producers) and a control group using different methods, suitable for field studies. SUBJECTS AND METHODS: Health-related complaints were examined and several functional tests, such as expirogram, olfactory threshold test, acoustic rhinometry, nasal lavage with biomarkers of inflammation (eosinophilic cationic proteins (ECP), myeloperoxidase (MPO), tryptase, albumin) and allergy tests were performed. The different tests were correlated to nasal complaints and to each other. RESULTS: Nasal blockage complaints were more common among farmers; overall, nasal polyps were more frequent in grain producers. Objective parameters showed more pronounced mucosal swelling in farmers and higher concentrations of ECP in nasal lavage compared with controls. Lung function, olfactory threshold, atopy frequency and allergen-specific IgE to the storage mite Lepidoglyphus destructor did not differ between farmers and controls. Mucosal swelling measured with acoustic rhinometry was more pronounced in subjects with nasal complaints, hypersensitivity, nasal polyps and symptoms from lower airways. There was a correlation between biomarkers in nasal lavage (MPO, albumin and ECP).
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13.
  • Kack, Ulrika, et al. (författare)
  • Nasal upregulation of CST1 in dog-sensitised children with severe allergic airway disease
  • 2021
  • Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The clinical presentation of children sensitised to dog dander varies from asymptomatic to severe allergic airway disease, but the genetic mechanisms underlying these differences are not clear. The objective of the present study was to investigate nasal transcriptomic profiles associated with dog dander sensitisation in school children and to reveal clinical symptoms related with these profiles. Methods: RNA was extracted from nasal epithelial cell brushings of children sensitised to dog dander and healthy controls. Blood sample analyses included IgE against dog dander, dog allergen molecules, other airborne and food allergens, basophil activation and white blood cell counts. Clinical history of asthma and rhinitis was recorded, and lung function was assessed (spirometry, methacholine provocation and exhaled nitric oxide fraction). Results: The most overexpressed gene in children sensitised to dog dander compared to healthy controls was CST1, coding for Cystatin 1. A cluster of these children with enhanced CST1 expression showed lower forced expiratory volume in 1 s, increased bronchial hyperreactivity, pronounced eosinophilia and higher basophil allergen threshold sensitivity compared with other children sensitised to dog dander. In addition, multi-sensitisation to lipocalins was more common in this group. Conclusions: Overexpression of CST1 is associated with more severe allergic airway disease in children sensitised to dog dander. CST1 is thus a possible biomarker of the severity of allergic airway disease and a possible therapeutic target for the future treatment of airborne allergy.
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14.
  • Kere, Maura, et al. (författare)
  • Exploring proteomic plasma biomarkers in eosinophilic and neutrophilic asthma
  • 2023
  • Ingår i: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 53:2, s. 186-197
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Few biomarkers identify eosinophilic and neutrophilic asthma beyond cell concentrations in blood or sputum. Finding novel biomarkers for asthma endotypes could give insight about disease mechanisms and guide tailored treatment. Our aim was to investigate clinical characteristics and inflammation-related plasma proteins in relation to blood eosinophil and neutrophil concentrations in subjects with and without asthma.METHODS: We included 24-26-year-old subjects (n = 2063) from the Swedish population-based cohort BAMSE. Subjects with asthma (n = 239) and without asthma (n = 1824) were subdivided based on blood eosinophil and neutrophil concentrations (cut-offs 0.3 × 109 /L and 5.0 × 109 /L, respectively). We measured the levels of 92 plasma proteins using Olink Proseek Multiplex Inflammation Panel Assay. Group statistics tests were used to analyse the data, as well as adjusted multiple logistic regression models.RESULTS: Among subjects with asthma, 21.8% had eosinophilic asthma and 20.5% neutrophilic asthma. Eosinophilic asthma, but not neutrophilic asthma, was associated with a distinct clinical phenotype with, for example, higher proportions of eczema and sensitization. Most plasma proteins that associated with high eosinophil and/or neutrophil blood concentrations in subjects with asthma showed similar associations in subjects without asthma. However, out of these proteins, MMP10 levels were associated with eosinophilic asthma and were significantly higher as compared to controls with high eosinophilic concentration, while CCL4 levels associated with high neutrophil concentration only in subjects with asthma.CONCLUSIONS: Eosinophilic asthma was associated with a clear clinical phenotype. With our definitions, we identified MMP10 as a possible plasma biomarker for eosinophilic asthma and CCL4 was linked to neutrophilic asthma. These proteins should be evaluated further in clinical settings and using sputum granulocytes to define the asthma endotypes.
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15.
  • Khaitov, Musa, et al. (författare)
  • Recombinant PreS-fusion protein vaccine for birch pollen and apple allergy
  • 2024
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - 0105-4538 .- 1398-9995. ; 79:4, s. 1001-1017
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: IgE cross-sensitization to major birch pollen allergen Bet v 1 and pathogenesis-related (PR10) plant food allergens is responsible for the pollen-food allergy syndrome.Methods: We designed a recombinant protein, AB-PreS, consisting of non-allergenic peptides derived from the IgE-binding sites of Bet v 1 and the cross-reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB-PreS was expressed in E. coli and purified by chromatography. The allergenic and inflammatory activity of AB-PreS was tested using basophils and PBMCs from birch pollen allergic patients. The ability of antibodies induced by immunization of rabbits with AB-PreS and birch pollen extract-based vaccines to inhibit allergic patients IgE binding to Bet v 1 and Mal d 1 was assessed by ELISA.Results: IgE-binding experiments and basophil activation test revealed the hypoallergenic nature of AB-PreS. AB-PreS induced lower T-cell activation and inflammatory cytokine production in cultured PBMCs from allergic patients. IgG antibodies induced by five injections with AB-PreS inhibited allergic patients' IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract-based vaccines. Additionally, immunization with AB-PreS induced HBV-specific antibodies potentially protecting from infection with HBV.Conclusion: The recombinant AB-PreS-based vaccine is hypoallergenic and superior over currently registered allergen extract-based vaccines regarding the induction of blocking antibodies to Bet v 1 and Mal d 1 in animals.
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17.
  • Konradsen, Jon R, et al. (författare)
  • Allergy to furry animals : new insights, diagnostic approaches, and challenges
  • 2015
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 135:3, s. 616-625
  • Tidskriftsartikel (refereegranskat)abstract
    • The prevalence of allergy to furry animals has been increasing, and allergy to cats, dogs, or both is considered a major risk factor for the development of asthma and rhinitis. An important step forward in the diagnosis of allergy to furry animals has been made with the introduction of molecular-based allergy diagnostics. A workshop on furry animals was convened to provide an up-to-date assessment of our understanding of (1) the exposure and immune response to the major mammalian allergens, (2) the relationship of these responses (particularly those to specific proteins or components) to symptoms, and (3) the relevance of these specific antibody responses to current or future investigation of patients presenting with allergic diseases. In this review research results discussed at the workshop are presented, including the effect of concomitant exposures from other allergens or microorganisms, the significance of the community prevalence of furry animals, molecular-based allergy diagnostics, and a detailed discussion of cat and dog components.
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19.
  • Käck, Ulrika, et al. (författare)
  • Molecular allergy diagnostics refine characterization of children sensitized to dog dander
  • 2018
  • Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 142:4, s. 1113-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sensitization to dog dander is an important risk factor for rhinoconjunctivitis and asthma but is not sufficient for diagnosing dog allergy. Molecular allergy diagnostics offer new opportunities for refined characterization. Objectives: We sought to study the association between sensitization to all presently known dog allergen components and clinical symptoms of dog allergy in children evaluated by using nasal provocation tests (NPTs). Methods: Sixty children (age, 10-18 years) sensitized to dog dander extract underwent NPTs with dog dander extract. Measurement of IgE levels to dog dander and to Can f 1, Can f 2, Can f 3, and Can f 5 was performed with ImmunoCAP, and measurement of IgE levels to Can f 4 and Can f 6 was performed with streptavidin ImmunoCAP. An IgE level of 0.1 kU(A)/L or greater was considered positive. Results: There was an association between sensitization to an increasing number of dog allergen components and a positive nasal challenge result (P = .01). Sensitization to lipocalins (odds ratio [OR], 6.0; 95% CI, 1.04-34.5), in particular Can f 4 (OR, 6.80; 95% CI 1.84-25.2) and Can f 6 (OR, 5.69; 95% CI, 1.59-20.8), was associated with a positive NPT result. Monosensitization to Can f 5 was related to a negative NPT result (OR, 5.78; 95% CI, 1.01-33.0). Conclusion: Sensitization to an increasing number of dog allergen components and to lipocalins is associated with dog allergy. Monosensitization to Can f 5 should not be regarded primarily as a marker for dog allergy.
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20.
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21.
  • Källström, Eva, et al. (författare)
  • Decreased frequency of intracellular IFN-gamma producing T cells in whole blood preparations from patients with atopic dermatitis.
  • 2002
  • Ingår i: Experimental Dermatology. - : Wiley. - 0906-6705. ; 11:6, s. 556-563
  • Tidskriftsartikel (refereegranskat)abstract
    • There have been contradictory reports on the shift in the T-cell cytokine expression pattern of peripheral blood mononuclear cells from patients with atopic dermatitis (AD); more specifically the interleukin (IL)-4 and interferon (IFN)-gamma profiles. The aim of this study was to shed further light on this contradiction by measuring the intracellular cytokines IL-4 and IFN-gamma by flow cytometry on unseparated whole blood to obtain results that, as accurately as possible, reflect the situation in circulating cells in vivo. The patient group including 64 patients with AD was compared with 18 nonatopic healthy adults. The results showed that the percentage of CD4+ T cells expressing IFN-gamma was significantly decreased (P <= 0.001), as well as the percentage expressing IL-4 (P < 0.05) in AD patients compared with healthy controls. Furthermore, in supernatants from whole blood samples stimulated with phorbol 12-myristate 13-acetate and ionomycin, production of IFN-gamma was significantly decreased, while IL-4 production remained unchanged in AD patients compared with healthy controls. We also investigated if there was a relationship between serum IgE level and Phadiatop®, a screening test for atopy, vs. the levels of IL-4 and IFN-gamma , but found no correlation with either. However, there was a significant correlation between disease severity and the level of total IgE (r = 0.67, P < 0.05). In conclusion, our results support the evidence for a decreased ability of peripheral CD4+ T cells to produce IFN-gamma among AD patients.
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22.
  • Lindqvist, Magnus, et al. (författare)
  • Natural course of pollen-induced allergic rhinitis from childhood to adulthood : A 20-year follow up.
  • 2023
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - 0105-4538 .- 1398-9995.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Allergic rhinitis (AR) is one of the most common chronic diseases worldwide. There are limited prospective long-term data regarding persistency and remission of AR. The objective of this study was to investigate the natural course of pollen-induced AR (pollen-AR) over 20 years, from childhood into early adulthood.METHODS: Data from 1137 subjects in the Barn/Children Allergi/Allergy Milieu Stockholm Epidemiologic birth cohort (BAMSE) with a completed questionnaire regarding symptoms, asthma, treatment with allergen immunotherapy (AIT) and results of allergen-specific IgE for inhalant allergens at 4, 8, 16 and 24 years were analyzed. Pollen-AR was defined as sneezing, runny, itchy or blocked nose; and itchy or watery eyes when exposed to birch and/or grass pollen in combination with allergen-specific IgE ≥0.35kUA /L to birch and/or grass.RESULTS: Approximately 75% of children with pollen-AR at 4 or 8 years had persistent disease up to 24 years, and 30% developed asthma. The probability of persistency was high already at low levels of pollen-specific IgE. The highest rate of remission from pollen-AR was seen between 16 and 24 years (21.5%); however, the majority remained sensitized. This period was also when pollen-specific IgE-levels stopped increasing and the average estimated annual incidence of pollen-AR decreased from 1.5% to 0.8% per year.CONCLUSION: Children with pollen-AR are at high risk of persistent disease for at least 20 years. Childhood up to adolescence seems to be the most dynamic period of AR progression. Our findings underline the close cross-sectional and longitudinal relationship between sensitization, AR and asthma.
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23.
  • Lundstrom, Susanna L., et al. (författare)
  • Allergic Asthmatics Show Divergent Lipid Mediator Profiles from Healthy Controls Both at Baseline and following Birch Pollen Provocation
  • 2012
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3
  • 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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24.
  • Melén, Erik, et al. (författare)
  • Air pollution and IgE sensitization in 4 European birth cohorts : the MeDALL project
  • 2021
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 147:2, s. 713-722
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWhether long-term exposure air to pollution has effects on allergic sensitization is controversial.ObjectiveOur aim was to investigate associations of air pollution exposure at birth and at the time of later biosampling with IgE sensitization against common food and inhalant allergens, or specific allergen molecules, in children aged up to 16 years.MethodsA total of 6163 children from 4 European birth cohorts participating in the Mechanisms of the Development of ALLergy [MeDALL] consortium were included in this meta-analysis of the following studies: Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) (Sweden), Influences of Lifestyle-Related Factors on the Human Immune System and Development of Allergies in Childhood (LISA)/German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development (GINIplus) (Germany), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA) (The Netherlands). The following indicators were modeled by land use regression: individual residential outdoor levels of particulate matter with aerodynamic diameters less than 2.5 μm, less than 10 μm, and between 2.5 and 10 μm; PM2.5 absorbance (a measurement of the blackness of PM2.5 filters); and nitrogen oxides levels. Blood samples drawn at ages 4 to 6 (n = 5989), 8 to 10 (n = 6603), and 15 to 16 (n = 5825) years were analyzed for IgE sensitization to allergen extracts by ImmunoCAP. Additionally, IgE against 132 allergen molecules was measured by using the MedALL microarray chip (n = 1021).ResultsAir pollution was not consistently associated with IgE sensitization to any common allergen extract up to age 16 years. However, allergen-specific analyses suggested increased risks of sensitization to birch (odds ratio [OR] = 1.12 [95% CI = 1.01-1.25] per 10-μg/m3 increase in NO2 exposure). In a subpopulation with microarray data, IgE to the major timothy grass allergen Phleum pratense 1 (Phl p 1) and the cat allergen Felis domesticus 1 (Fel d 1) greater than 3.5 Immuno Solid-phase Allergen Chip standardized units for detection of IgE antibodies were related to PM2.5 exposure at birth (OR = 3.33 [95% CI = 1.40-7.94] and OR = 4.98 [95% CI = 1.59-15.60], respectively, per 5-μg/m3 increase in exposure).ConclusionAir pollution exposure does not seem to increase the overall risk of allergic sensitization; however, sensitization to birch as well as grass pollen Phl p 1 and cat Fel d 1 allergen molecules may be related to specific pollutants.
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25.
  • Melen, Erik, et al. (författare)
  • Male sex is strongly associated with IgE-sensitization to airborne but not food allergens : results up to age 24 years from the BAMSE birth cohort
  • 2020
  • Ingår i: Clinical and Translational Allergy. - : BioMed Central. - 2045-7022. ; 75, s. 161-162
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up to half of the population in high-income countries has allergen-specific IgE antibodies. However, data regarding sex differences of IgE-sensitization from childhood to adulthood is limited. Objective To explore IgE-sensitization to common foods and airborne allergens in relation to sex over time in a population-based cohort followed up to young adulthood. Methods The Swedish population-based birth cohort BAMSE includes 4089 subjects who have been followed regularly with questionnaires and clinical investigations. A recent 24-year follow-up included 3069 participants (75%). Sera collected at 4, 8, 16 and 24 years were analyzed for IgE-antibodies to 14 common foods and airborne allergens. Results At 24 years sensitization to foods had decreased compared to previous follow-ups affecting 8.4%, while sensitization to airborne allergens was more common, affecting 42.2%. Male sex was associated with IgE-sensitization to airborne allergens at all ages (overall OR: 1.68, 95% CI 1.46-1.94) while there was no statistically significant association between sex and sensitization to food allergens (overall OR: 1.10, 95% CI 0.93-1.32). Levels of allergen-specific IgE did not differ significantly between males and females for any of the tested foods or airborne allergens at any age, following adjustment for multiple comparisons. Conclusion IgE-sensitization to airborne allergens increases with age up to young adulthood, whereas sensitization to food allergens seems to level off. Male sex is strongly associated with IgE-sensitization to airborne allergens from early childhood up to young adulthood. In contrast, there is little evidence for associations between sex and IgE-sensitization to foods.
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26.
  • Mitselou, Niki, 1982-, et al. (författare)
  • Preterm birth reduces the risk of IgE sensitization up to early adulthood : A population-based birth cohort study
  • 2022
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Munksgaard Forlag. - 0105-4538 .- 1398-9995. ; 77:5, s. 1570-1582
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Immunoglobulin E (IgE) sensitization is associated with asthma and allergic diseases. Gestational age influences early immune system development, thereby potentially affecting the process of tolerance induction to allergens.Objective: To study IgE sensitization to common allergens by gestational age from childhood up to early adulthood.Methods: Population-based birth cohort, data from the Swedish BAMSE study were used. Allergen-specific IgE antibodies to a mix of common food (fx5) and inhalant (Phadiatop) allergens were analysed at 4, 8, 16 and 24 years. Sensitization was defined as allergen-specific IgE >= 0.35 kU(A)/L to fx5 and/or Phadiatop at each time point. Using logistic regression and generalized estimated equations, adjusted odds ratios (aORs) for sensitization in relation to gestational age were calculated. Replication was sought within the Swedish twin study STOPPA.Results: In BAMSE, 3522 participants were screened for IgE antibodies during follow-up; of these, 197 (5.6%) were born preterm (<37 gestational weeks) and 330 (9.4%) post-term (>= 42 weeks). Preterm birth reduced the risk of sensitization to common food and/or inhalant allergens up to early adulthood by 29% (overall aOR = 0.71; 95% CI: 0.52-0.98), and to food allergens specifically by 40% (overall aOR = 0.60; 95% CI: 0.38-0.93). No relation was found between post-term birth and IgE sensitization at any time point. Replication analyses in STOPPA (N = 675) showed similar risk estimates for sensitization to food and/or inhalant allergens (aOR = 0.72; 95% CI: 0.42-1.21), which resulted in a combined meta-analysis aOR = 0.71 (95% CI: 0.54-0.94).Conclusions: Our study suggests an inverse association between preterm birth and long-term IgE sensitization.
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27.
  • Nilsson, Ola B., et al. (författare)
  • Designing a Multimer Allergen for Diagnosis and Immunotherapy of Dog Allergic Patients
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:10
  • 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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28.
  • Nilsson, Ola B., et al. (författare)
  • Mammalian-derived respiratory allergens - Implications for diagnosis and therapy of individuals allergic to furry animals
  • 2014
  • Ingår i: Methods. - : Elsevier BV. - 1046-2023 .- 1095-9130. ; 66:1, s. 86-95
  • 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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29.
  • Protudjer, Jennifer L. P., et al. (författare)
  • Milk-Related Symptoms and Immunoglobulin E Reactivity in Swedish Children from Early Life to Adolescence
  • 2018
  • Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 10:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Cow's milk often causes symptoms in infants. Whereas, some continue to experience symptoms through childhood, others become tolerant. Yet, the ages at which persistence and tolerance occur are less clear. Thus, we examined the age of onset and persistence of milk-related symptoms from early life to adolescence, and Immunoglobulin E (IgE) milk reactivity, focusing on gender differences in a large, population-based birth cohort. Overall, 20.0% (537/2985) of children, with a comparable gender distribution, had early life milk-related symptoms. At 16y, approximately 2% (62/2985) children had persistent symptoms and high milk IgE levels (e.g., median at 4 years: 1.5 kU(A)/L) that were beginning in early life. In contrast, 94% had transient symptoms and low median IgE levels (early life: 0.63 kU(A)/L, 8y: 0.72 kU(A)/L; 16 years: 1.1 kU(A)/L). Also, at 16 years, approximately 6% of females and 3% of males without any previously reported symptoms reported adolescent-onset of symptoms (p < 0.001). Such symptoms were almost exclusively gastrointestinal symptoms and were not associated with detectable IgE. In conclusion, early life milk-related symptoms are common, although most cases are transient by 16 years. Twice as many females vs. males report adolescent-onset symptoms, and particularly gastrointestinal symptoms. Children with persistent symptoms have both a higher prevalence and higher milk IgE levels, as compared to other phenotypes.
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30.
  • Ramos-Ramirez, Patricia, et al. (författare)
  • House Dust Mite and Cat Dander Extract Induce Asthma-Like Histopathology with an Increase of Mucosal Mast Cells in a Guinea Pig Model
  • 2023
  • Ingår i: Journal of Immunology Research. - : Hindawi Publishing Corporation. - 2314-8861 .- 2314-7156. ; 2023
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Asthma is a chronic inflammatory disease with structural changes in the lungs defined as airway remodelling. Mast cell responses are important in asthma as they, upon activation, release mediators inducing bronchoconstriction, inflammatory cell recruitment, and often remodelling of the airways. As guinea pigs exhibit anatomical, physiological, and pharmacological features resembling human airways, including mast cell distribution and mediator release, we evaluated the effect of extracts from two common allergens, house dust mite (HDM) and cat dander (CDE), on histopathological changes and the composition of tryptase- and chymase-positive mast cells in the guinea pig lungs. Methods. Guinea pigs were exposed intranasally to HDM or CDE for 4, 8, and 12 weeks, and airway histology was examined at each time point. Hematoxylin and eosin, Picro-Sirius Red, and Periodic Acid-Schiff staining were performed to evaluate airway inflammation, collagen deposition, and mucus-producing cells. In addition, Astra blue and immunostaining against tryptase and chymase were used to visualize mast cells. Results. Repetitive administration of HDM or CDE led to the accumulation of inflammatory cells into the proximal and distal airways as well as increased airway smooth muscle mass. HDM exposure caused subepithelial collagen deposition and mucus cell hyperplasia at all three time points, whereas CDE exposure only caused these effects at 8 and 12 weeks. Both HDM and CDE induced a substantial increase in mast cells after 8 and 12 weeks of challenges. This increase was primarily due to mast cells expressing tryptase, but not chymase, thus indicating mucosal mast cells. Conclusions. We here show that exposure to HDM and CDE elicits asthma-like histopathology in guinea pigs with infiltration of inflammatory cells, airway remodelling, and accumulation of primarily mucosal mast cells. The results together encourage the use of HDM and CDE allergens for the stimulation of a clinically relevant asthma model in guinea pigs.
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31.
  • Sdona, Emmanouela, et al. (författare)
  • Dietary fibre in relation to asthma, allergic rhinitis and sensitization from childhood up to adulthood
  • 2022
  • Ingår i: Clinical and Translational Allergy. - : John Wiley & Sons. - 2045-7022. ; 12:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Dietary fibre may reduce the risk of allergy. Our aim was to investigate the association between fibre intake in childhood, asthma, allergic rhinitis and IgE sensitization up to adulthood.Methods: The individual fibre intake of 2285 participants from the Swedish population-based birth cohort BAMSE was estimated between 98- and 107-item food frequency questionnaires at ages 8 and 16 years, respectively. At 8, 16 and 24 years, asthma and allergic rhinitis symptoms were assessed by questionnaires, and sensitization to common allergens by serum IgE. Longitudinal associations were analysed by generalized estimating equations, adjusting for potential confounders.Results: An inverse overall association was indicated between fibre intake at 8 years and allergic rhinitis symptoms up to 24 years (OR per 5 g/d 0.86; 95% CI 0.77-0.96), particularly in combination with airborne (0.74; 0.62-0.89) and food (0.69; 0.54-0.88) allergen sensitization. Higher fibre intake was also associated with specific allergen sensitization, for example, birch (0.77; 0.67-0.88) and soy (0.68; 0.53-0.87). No association was observed with asthma. Regarding sources, fruit (0.79; 0.67-0.94) and other (potatoes, chips/popcorn, legumes, and nuts, 0.71; 0.50-0.99), but not cereal or vegetable fibre were associated with allergic rhinitis. In additional analyses, including long-term fibre intake at 8 and 16 years, excluding participants with food-related allergic symptoms to examine reverse causation, as well as adjusting for antioxidant intake, associations were attenuated and became non-significant.Conclusion: Higher fibre intake in mid-childhood may be inversely associated with allergic rhinitis and sensitization to specific allergens up to adulthood. However, avoidance of food triggers of allergic symptoms in allergic rhinitis patients may contribute to the protective associations.
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32.
  • Swedin, Linda, et al. (författare)
  • Dissociation of airway inflammation and hyperresponsiveness by cyxloogynease inhibition in allergen challenged mice
  • 2009
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 34:1, s. 200-208
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the current study was to define how cyclooxygenase (COX)-activity affects airway hyperresponsiveness (AHR) and inflammation using interventions with COX inhibitors at different time points during allergen challenge and/or prior to measurement of AHR in an eosinophil-driven allergic mouse model. Inflammatory cells were assessed in bronchioalveolar lavage (BAL) and AHR was evaluated as the total lung resistance to methacholine (MCh) challenge. Administration of FR122047 (COX-1 inhibitor) during ovalbumin (OVA) challenge and prior to MCh challenge enhanced AHR without affecting the inflammatory cell response. In contrast, administration of lumiracoxib (COX-2 inhibitor) during the same time period had no effect on AHR but reduced the inflammatory cells in BAL. Nonselective COX inhibition with diclofenac both enhanced the AHR and reduced the inflammatory cells. Administration of diclofenac only during OVA challenge reduced the cells in BAL without any changes in AHR, whereas administration of diclofenac only prior to MCh challenge enhanced AHR but did not affect the cells in BAL. The present study implicates distinct roles of prostanoids generated along the COX-1 and COX-2 pathways and, furthermore, that inflammatory cells in BAL do not change in parallel with AHR. These findings support the fact that AHR and the inflammatory response are distinct and, at least in part, uncoupled events.
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33.
  • Tedner, Sandra G., et al. (författare)
  • Development of sensitization to peanut and storage proteins and relation to markers of airway and systemic inflammation : A 24-year follow-up
  • 2023
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 78:2, s. 488-499
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundLong-time data of peanut allergy over time is sparse. We aimed to study the longitudinal development of sensitization to peanut extract and storage protein allergen molecules and associations with asthma status, airway and systemic inflammation markers.MethodsThe Swedish birth cohort BAMSE followed 4089 participants with questionnaires, clinical investigations and blood sampling between 0 and 24 years. Information on (i) background factors at 2 months, (ii) peanut allergy symptoms and IgE data (ImmunoCAP) at 4, 8, 16, and 24 years, and (iii) IgE to storage proteins, lung function data including exhaled nitric oxide (FENO) as well as systemic inflammatory markers at 24 years of age were collected.ResultsThe prevalence of peanut extract sensitization, defined as IgE ≥ 0.35 kUA/L, was 5.4%, 8.0%, 7.5%, and 6.2% at 4, 8, 16, and 24 years of age, respectively. Between 8 and 24 years of age, (33/1565) participants developed IgE-ab to peanut extract (median 1,4, range 0.7–2.6 kUA/L), and among those 85% were also sensitized to birch. Only six individuals developed sensitization to Ara h 2 (≥0.1 kUA/L) between 8 and 24 years of age, of whom three had an IgE-ab level between 0.1–0.12 kUA/L. Storage protein sensitization was associated with elevated FENO, blood eosinophils and type 2 inflammation-related systemic proteins.ConclusionSensitization to peanut extract after 4 years of age is mainly induced by birch cross-sensitization and IgE to Ara h 2 rarely emerges after eight years of age. Storage protein sensitization is associated with respiratory and systemic inflammation.
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34.
  • Tedner, Sandra G., et al. (författare)
  • Extract and molecular-based early infant sensitization and associated factors-A PreventADALL study
  • 2021
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:9, s. 2730-2739
  • Tidskriftsartikel (refereegranskat)abstract
    • Background More knowledge about sensitization patterns in early infancy, including impact of molecular allergology, is needed to help predict future allergy development more accurately. Objective We aimed to determine the prevalence and patterns of allergic sensitization at 3 months of age, and explore possible associated factors. Methods From the Scandinavian antenatally recruited PreventADALL mother-child cohort, we included 1110 3-month infants with available serum. Sensitization was defined as s-IgE of >= 0.1 kU(A)/L by Phadiatop Infant(R) (ThermoFisher Scientific) including birch, cat, grass, dog, milk, egg, peanut and wheat. Further ImmunoCAP analyses to ovomucoid, casein, Ara h 1-3, omega-5-gliadin were performed in food extract s-IgE-positive children. Maternal sensitization was defined as s-IgE >= 0.35 kU(A)/L to Phadiatop(R) (inhalant allergen mix) and/or Fx5 (food allergen mix) at 18-week pregnancy. Results Overall 79 (7.3%) infants had specific sensitization, many with low s-IgE-levels (IQR 0.16-0.81 kU(A)/L), with 78 being sensitized to food extract allergens; 41 to egg, 27 to milk, 10 to peanut, and 25 to wheat. A total of 62/78 were further analysed, 18 (29%) had s-IgE to ovomucoid, casein, Ara h 1-3 and/or omega-5-gliadin. Eight infants (0.7%) were sensitized to inhalant allergens. Maternal sensitization to food allergens was associated with infant sensitization, odds ratio 3.64 (95% CI 1.53-8.68). Conclusion Already at 3 months of age, 7% were sensitized to food, mostly without detectable s-IgE to food allergen molecules, and <1% to inhalant allergens. Maternal food sensitization was associated with infants' sensitization.
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35.
  • Thacher, Jesse D, et al. (författare)
  • Parental smoking and development of allergic sensitization from birth to adolescence
  • 2016
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 71:2, s. 239-248
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The relation between secondhand tobacco smoke (SHS) exposure and the development of allergic sensitization in children is unclear. The aim of this study was to determine whether maternal smoking during pregnancy and postnatal SHS exposure contributes to the development of allergic sensitization in children and adolescents up to 16 years of age.METHODS: We included 3316 children from a birth cohort followed for 16 years. SHS exposure and symptoms of allergic disease were assessed using repeated parental questionnaires. Serum immunoglobulin E against eight common inhalant and six food allergens was assessed at ages 4, 8, and 16 years with ImmunoCAP. The association between SHS exposure and sensitization was explored using logistic regression and generalized estimating equations.RESULTS: Exposure to SHS in infancy without prior exposure in utero, was associated with an excess risk of food sensitization at age 4 (OR 1.47, 95% CI 1.08-2.00), with comparable ORs at ages 8 and 16 years. In longitudinal analyses, an overall association was indicated between SHS in infancy and food sensitization up to age 16 years (OR 1.24, 95% CI 0.98-1.56). Maternal smoking during pregnancy was unrelated to sensitization up to 16 years of age. When sensitization was combined with concurrent symptoms of allergic disease, SHS in infancy was associated with an overall elevated risk of eczema with sensitization (OR 1.62, 95% CI 1.20-2.18).CONCLUSIONS: SHS exposure in infancy appears to increase the risk of sensitization to food allergens up to age 16 years as well as eczema in combination with sensitization.
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36.
  • Thörnqvist, Linnea, et al. (författare)
  • Linear Epitope Binding Patterns of Grass Pollen-Specific Antibodies in Allergy and in Response to Allergen-Specific Immunotherapy
  • 2022
  • Ingår i: Frontiers in Allergy. - : Frontiers Media SA. - 2673-6101. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergic diseases affect many individuals world-wide and are dependent on the interaction between allergens and antibodies of the IgE isotype. Allergen-specific immunotherapy (AIT) can alter the development of the disease, e.g., through induction of allergen-specific IgG that block allergen-IgE interactions. The knowledge of epitopes recognized by allergy-causing and protective antibodies are limited. Therefore, we developed an allergome-wide peptide microarray, aiming to track linear epitope binding patterns in allergic diseases and during AIT. Here, we focused on immune responses to grass pollen allergens and found that such epitopes were commonly recognized before initiation of AIT and that AIT commonly resulted in increased antibody production against additional epitopes already after 1 year of treatment. The linear epitope binding patterns were highly individual, both for subjects subjected to and for individuals not subjected to AIT. Still, antibodies against some linear epitopes were commonly developed during AIT. For example, the two rigid domains found in grass pollen group 5 allergens have previously been associated to a diversity of discontinuous epitopes. Here, we present evidence that also the flexible linker, connecting these domains, contains regions of linear epitopes against which antibodies are developed during AIT. We also describe some commonly recognized linear epitopes on Phl p 2 and suggest how antibodies against these epitopes may contribute to or prevent allergy in relation to a well-defined stereotyped/public IgE response against the same allergen. Finally, we identify epitopes that induce cross-reactive antibodies, but also antibodies that exclusively bind one of two highly similar variants of a linear epitope. Our findings highlight the complexity of antibody recognition of linear epitopes, with respect to both the studied individuals and the examined allergens. We expect that many of the findings in this study can be generalized also to discontinuous epitopes and that allergen peptide microarrays provide an important tool for enhancing the understanding of allergen-specific antibodies in allergic disease and during AIT.
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37.
  • Tjernberg, Ivar, et al. (författare)
  • IgE reactivity to alpha-Gal in relation to Lyme borreliosis
  • 2017
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background An association between tick bites, the development of immunoglobulin E (IgE) antibodies to galactose-alpha-1, 3-galactose (alpha-Gal) and red meat allergy has recently been reported. Here we wanted to elucidate the relation between tick exposure, IgE antibodies to alpha-Gal and Lyme borreliosis (LB). Methods In the highly LB endemic area of Kalmar County, Sweden, serum samples and health inquiries from 518 blood donors were included. All sera were investigated for multiple IgG antiBorrelia antibodies using a multiplex assay (recomBead, Mikrogen). In addition, three serially collected sera over a six month period from 148 patients with clinically defined erythema migrans (EM) were included. IgE antibodies against alpha-Gal were determined using ImmunoCAP (Thermo Fisher Scientific). Results In blood donors reporting previous LB (n = 124) IgE to alpha-Gal was found in 16%, while in donors denying previous LB but with multiple anti-Borrelia antibodies (n = 94; interpreted as asymptomatic LB) 10% were IgE alpha-Gal-positive. Finally, in donors without Borrelia antibodies denying previous LB (n = 300) 14% showed IgE to alpha-Gal. No significant difference in proportions among the groups were found. In EM patients, IgE to alpha-Gal was found in 32/148 (22%) at diagnosis, 31/148 (21%) after two-three months and 23/148 (16%) after six months. A significant reduction of proportion and level of IgE to alpha-Gal was found between the second and third sample (pamp;lt; 0.01). A positive IgE anti alpha-Gal was more common among men compared with women both in blood donors and in EM patients (p amp;lt;= 0.01). Conclusions IgE to alpha-Gal reactivity was common in a tick endemic area but showed no significant relation to previous LB. IgE anti-alpha-Gal reactivity in EM patients peaked within three months of diagnosis of EM, after which it waned indicating that recent tick exposure is of importance in alpha-Gal sensitization. Furthermore, IgE anti alpha-Gal was more common in men compared with women.
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38.
  • Velickovic, Tanja Cirkovic, et al. (författare)
  • Low levels of endotoxin enhance allergen-stimulated proliferation and reduce the threshold for activation in human peripheral blood cells
  • 2008
  • Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 146:1, s. 1-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Endotoxins, comprised of bacterial cell wall lipopolysaccharides (LPS), have been reported to have both protective and exacerbating effects on the development and maintenance of allergic disease in humans and on markers of allergic inflammation in animal models of allergy. In this study, we investigated the effect of low concentrations of LPS on human peripheral blood mononuclear cells (PBMC) stimulated with the major cat allergen Fel d 1. Methods: Extensive purification of recombinant (r) Fel d 1 yielded essentially endotoxin-free rFel d 1 (0.2 ng LPS/mg protein). PBMCs prepared from 15 subjects having IgE to cat (>0.7 kU(A)/l) and 8 subjects IgE negative to cat were stimulated with 2, 10 or 25 mu g/ml of rFel d 1 in the presence or absence of 50 pg/ml LPS. Proliferation was measured after 7 days of culture and supernatants were analyzed for IFN gamma, IL-5 and IL-10. Results: LPS (50 pg/ml) increased rFel d 1-stimulated proliferation of PBMCs both from subjects IgE-positive and subjects negative to cat allergens. PBMCs from 13 of the subjects did not proliferate in response to stimulation with 2 and 10 mu g/ml rFel d 1 alone but did so in the presence of LPS. Moreover, LPS increased the levels of rFel d 1-stimulated IFN gamma in cultures from cat-negative subjects, IL-5 from cat-positive subjects and IL-10 from both groups. Conclusion: Very low doses of LPS enhance proliferation and decrease the apparent threshold level for cell activation, prompting careful evaluation of allergen stimulated T cell activation in vitro. Copyright (C) 2007 S. Karger AG, Basel.
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39.
  • Wang, Gang, et al. (författare)
  • Assessment of chronic bronchitis and risk factors in young adults : results from BAMSE
  • 2020
  • Ingår i: European Respiratory Journal. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 0903-1936 .- 1399-3003.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Chronic bronchitis is associated with substantial morbidity among elderly adults, but little is known about its prevalence and risk factors in young adults. Our aim was to assess the prevalence and early life risk factors for chronic bronchitis in young adults. METHODS: Questionnaire data and clinical measures from the 24-year follow-up of the Swedish BAMSE cohort were used. We assessed chronic bronchitis (CB) as the combination of cough and mucus production in the morning during winter. Environmental and clinical data from birth and onwards were used for analyses of risk factors. RESULTS: At the 24-year follow-up, 75% (n=3064) participants completed the questionnaire and 2030 performed spirometry. The overall prevalence of CB was 5.5% (n=158) with similar estimates in males and females. Forty-nine percent of CB cases experienced more than 3 self-reported respiratory infections in the last year compared to 18% in non-CB subjects (p<0.001), and 37% of cases were current smokers (versus 19%). Statistically significant lower post-FEV(1)/FVC were observed in CB compared to non-CB subjects (mean z-score -0.06 versus 0.13, p=0.027). Daily smoking (adjusted Odds Ratio, aOR=3.85, p<0.001), air pollution exposure (black carbon during ages 1-4 years old, aOR=1.71 per 1 μg·m(3) increase, p=0.009) and exclusive breast-feeding during four months or more (aOR=0.66, p=0.044) were associated with CB. CONCLUSION: Chronic bronchitis in young adults is associated with recurrent respiratory infections. Besides smoking, our results support role of early life exposures, such as air pollution and exclusive breast-feeding, for respiratory health later in life.
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40.
  • Wang, Gang, et al. (författare)
  • Early-life risk factors for reversible and irreversible airflow limitation in young adults : findings from the BAMSE birth cohort
  • 2021
  • Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 76:5, s. 503-507
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to determine prevalence and early-life risk factors for reversible and irreversible airflow limitation in young adults from the general population. Among young adults in their 20s, the prevalence was 5.3% for reversible airflow limitation and 2.0% for irreversible airflow limitation. While parental asthma was the only risk factor for development of reversible airflow limitation, the risk factors for development of irreversible airflow limitation were current asthma, childhood respiratory tract infections and asthma, and exposure to air pollution.
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41.
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42.
  • Wickman, Magnus, et al. (författare)
  • Detection of IgE Reactivity to a Handful of Allergen Molecules in Early Childhood Predicts Respiratory Allergy in Adolescence
  • 2017
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 26, s. 91-99
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sensitization in early childhood may precede respiratory allergy in adolescence.Methods: IgE reactivity against 132 allergen molecules was evaluated using the MeDALL microarray in sera obtained from a random sample of 786 children at the age of 4, 8 and 16 years in a population based birth cohort (BAMSE). Symptoms were analyzed by questionnaire at ages 4, 8 and 16 years. Clinically and independent relevant allergen molecules accounting for ≥ 90% of IgE reactivities in sensitized individuals and at all time-points were identified as risk molecules and used to predict respiratory allergy. The data was replicated in the Manchester Asthma and Allergy Study (MAAS) birth cohort by studying IgE reactivity with the use of a commercial IgE microarray. Sera were obtained from children at the ages of 3, 5, 8 and 11 years (N = 248) and the outcome was studied at 11 years.Findings: In the BAMSE cohort 4 risk molecules could be identified, i.e.: Ara h 1 (peanut), Bet v 1 (birch), Fel d 1 (cat), Phl p 1 (grass). For MAAS the corresponding number of molecules was 5: Der p 1 (dust mite), Der f 2 (dust mite), Phl p 1 (grass), Phl p 5 (grass), Fel d 1 (cat). In BAMSE, early IgE reactivity to ≥ 3 of 4 allergen molecules at four years predicted incident and persistent asthma and/or rhinitis at 16 years (87% and 95%, respectively). The corresponding proportions in the MAAS cohort at 16 years were 100% and 100%, respectively, for IgE reactivity to ≥ 3 of 5 risk molecules.Interpretations: IgE reactivity to a few allergen molecules early in life identifies children with a high risk of asthma and/or rhinitis at 16 years. These findings will be of importance for developing preventive strategies for asthma and rhinitis in children.
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43.
  • Wärnberg Gerdin, Sabina, et al. (författare)
  • Impaired skin barrier and allergic sensitization in early infancy
  • 2022
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 77:5, s. 1464-1476
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Factors predicting allergic sensitization in the first 6 months of life are poorly understood. We aimed to determine whether eczema, dry skin, and high transepidermal water loss (TEWL) at 3 months were associated with allergic sensitization at 6 months of age and, secondarily, to establish whether these characteristics predicted sensitization from 3 to 6 months of age.Methods: At 3 months of age, 1,994 infants from the population-based PreventADALL birth cohort in Norway and Sweden were assessed for eczema and dry skin on the cheeks and/or extensors; impaired skin barrier function, defined as TEWL in the upper quartile (>9.4 g/m(2)/h), and allergen-specific IgE levels <0.1 kU(A)/L, available in 830. At 6 months, we assessed allergic sensitization to any food (egg, cow's milk, peanut, wheat, soy) or inhalant (birch, timothy grass, dog, and cat) allergen by a skin prick test wheal diameter >= 2 mm larger than negative control.Results: Any sensitization was found in 198 of the 1,994 infants (9.9%), the majority to food allergens (n = 177, 8.9%). Eczema, dry skin, and high TEWL at 3 months increased the risk of sensitization at 6 months; adjusted odds ratios 4.20 (95% CI 2.93-6.04), 2.09 (95% CI 1.51-2.90) and 3.67 (95% CI 2.58-5.22), respectively. Eczema predicted sensitization with 55.6% sensitivity and 68.1% specificity; dry skin with 65.3% sensitivity and 57.3% specificity; and high TEWL with 61.7% sensitivity and 78.1% specificity.Conclusion: Eczema, dry skin, and high TEWL at 3 months predicted allergic sensitization at 6 months of age.
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