Publications by authors named "Thomas Hawranek"

41 Publications

Wheat Anaphylaxis in Adults Differs from Reactions to Other Types of Food.

J Allergy Clin Immunol Pract 2021 Apr 5. Epub 2021 Apr 5.

Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Electronic address:

Background: Wheat is one of the most commonly consumed foods and a known elicitor of anaphylaxis in children and adults. Reactions in adults are often cofactor dependent and characterized by a prolonged time between food intake and the onset of symptoms making the diagnosis of wheat anaphylaxis challenging.

Objective: To characterize a cohort of patients with the history of wheat anaphylaxis to better understand this atypical phenotype of anaphylaxis.

Methods: Data from the European Anaphylaxis Registry from 2007 to 2019 (n = 10,636) including 250 patients (213 adults and 37 children) with a history of anaphylaxis caused by wheat were analyzed.

Results: Wheat was the most common food elicitor of anaphylaxis in adults in the registry in Central Europe. Reactions to wheat in adults were frequently associated with exercise as a cofactor (82.8%) and partially delayed (57.5%). Only 36.9% of patients had atopic comorbidities, which was uncommonly low for adult patients allergic to other kinds of foods (63.2%). Anaphylaxis to wheat presented frequently with cardiovascular symptoms (86.7%) including severe symptoms such as loss of consciousness (41%) and less often with respiratory symptoms (53.6%). The reactions to wheat were more severe than reactions to other foods (odds ratio [OR] = 4.33), venom (OR = 1.58), or drugs (OR = 2.11).

Conclusions: Wheat is a relevant elicitor of anaphylaxis in adults in Central Europe. Wheat anaphylaxis is highly dependent on the presence of cofactors and less frequently associated with atopic diseases compared with other food allergies. More data on mechanisms of wheat-induced anaphylaxis are required to develop preventive measures for this potentially life-threatening disease.
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http://dx.doi.org/10.1016/j.jaip.2021.03.037DOI Listing
April 2021

Anaphylaxis in middle-aged patients.

Allergol Select 2021 23;5:133-139. Epub 2021 Mar 23.

Allergy and Immunology, Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Berlin.

Age is one of the most important factors influencing the course of anaphylaxis: moreover, the frequency of elicitors of anaphylaxis is age-associated. We analyzed 8,465 anaphylactic episodes in adult patients in three age groups with a focus on patients in the middle-age group (35 - 65 years old). Insect venom was the most frequent trigger in this age group (51.2%) followed by drugs (22.8%) and food (17.3%). Severe reactions were observed in 40.1% of middle-aged patients and occurred more frequently in this age group than in patients below 35 years (27.6%) and less frequently than in patients over 65 years (55.6%). The symptoms and comorbidity profile also changed with age, most significantly regarding the increase in rates of concomitant cardiologic diseases and (severe) cardiovascular symptoms.
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http://dx.doi.org/10.5414/ALX02216EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991893PMC
March 2021

β-blockers and ACE inhibitors are not a risk factor for severe systemic sting reactions and adverse events during venom immunotherapy.

Allergy 2021 Feb 19. Epub 2021 Feb 19.

Department of Internal Diseases, Pulmonology and Allergology, Medical University of Wroclaw, Wroclaw, Poland.

Background: There is controversy whether taking β-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT).

Methods: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment.

Results: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β-blockers, 11.9% ACEI, 5.0% β-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43-1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of β-blockers or ACEI (OR: 1.14, 95% CI: 0.89-1.46, p = 0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β-blockers, none an ACEI.

Conclusions: This trial provides robust evidence that taking β-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629).
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http://dx.doi.org/10.1111/all.14785DOI Listing
February 2021

High-affinity Bet v 1-specific secretory IgA antibodies in nasal fluids protect against birch pollen allergy.

Allergy 2021 Feb 16. Epub 2021 Feb 16.

Department of Biosciences, University of Salzburg, Salzburg, Austria.

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http://dx.doi.org/10.1111/all.14782DOI Listing
February 2021

Healthcare provision for insect venom allergy patients during the COVID-19 pandemic.

Allergo J Int 2020 8;29(8):257-261. Epub 2020 Dec 8.

Department and Outpatient Clinic for Dermatology and Allergology, University Hospital Munich, Munich, Germany.

The population prevalence of insect venom allergy ranges between 3-5%, and it can lead to potentially life-threatening allergic reactions. Patients who have experienced a systemic allergic reaction following an insect sting should be referred to an allergy specialist for diagnosis and treatment. Due to the widespread reduction in outpatient and inpatient care capacities in recent months as a result of the COVID-19 pandemic, the various allergy specialized centers in Germany, Austria, and Switzerland have taken different measures to ensure that patients with insect venom allergy will continue to receive optimal allergy care. A recent data analysis from the various centers revealed that there has been a major reduction in newly initiated insect venom immunotherapy (a 48.5% decline from March-June 2019 compared to March-June 2020: data from various centers in Germany, Austria, and Switzerland). The present article proposes defined organizational measures (e.g., telephone and video appointments, rearranging waiting areas and implementing hygiene measures and social distancing rules at stable patient numbers) and medical measures (collaboration with practice-based physicians with regard to primary diagnostics, rapid COVID-19 testing, continuing already-initiated insect venom immunotherapy in the outpatient setting by making use of the maximal permitted injection intervals, prompt initiation of insect venom immunotherapy during the summer season, and, where necessary, using outpatient regimens particularly out of season) for the care of insect venom allergy patients during the COVID-19 pandemic.
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http://dx.doi.org/10.1007/s40629-020-00157-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722411PMC
December 2020

Phenotype and risk factors of venom-induced anaphylaxis: A case-control study of the European Anaphylaxis Registry.

J Allergy Clin Immunol 2021 Feb 22;147(2):653-662.e9. Epub 2020 Jun 22.

Division of Allergy and Immunology, Department of Dermatology, Venerology, and Allergology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany. Electronic address:

Background: Venom-induced anaphylaxis (VIA) is a common, potentially life-threatening hypersensitivity reaction associated with (1) a specific symptom profile, 2) specific cofactors, and 3) specific management. Identifying the differences in phenotypes of anaphylaxis is crucial for future management guidelines and development of a personalized medicine approach.

Objective: This study aimed to evaluate the phenotype and risk factors of VIA.

Methods: Using data from the European Anaphylaxis Registry (12,874 cases), we identified 3,612 patients with VIA and analyzed their cases in comparison with sex- and age-matched anaphylaxis cases triggered by other elicitors (non-VIA cases [n = 3,605]).

Results: VIA more frequently involved more than 3 organ systems and was associated with cardiovascular symptoms. The absence of skin symptoms during anaphylaxis was correlated with baseline serum tryptase level and was associated with an increased risk of a severe reaction. Intramuscular or intravenous epinephrine was administered significantly less often in VIA, in particular, in patients without a history of anaphylaxis. A baseline serum tryptase level within the upper normal range (8-11.5 ng/mL) was more frequently associated with severe anaphylaxis.

Conclusion: Using a large cohort of VIA cases, we have validated that patients with intermediate baseline serum tryptase levels (8-11 ng/mL) and without skin involvement have a higher risk of severe VIA. Patients receiving β-blockers or angiotensin-converting enzyme inhibitors had a higher risk of developing severe cardiovascular symptoms (including cardiac arrest) in VIA and non-VIA cases. Patients experiencing VIA received epinephrine less frequently than did cases with non-VIA.
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http://dx.doi.org/10.1016/j.jaci.2020.06.008DOI Listing
February 2021

Anaphylaxis in Elderly Patients-Data From the European Anaphylaxis Registry.

Front Immunol 2019 24;10:750. Epub 2019 Apr 24.

Division of Allergology and Immunology, Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin Institute of Health, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Elicitors and symptoms of anaphylaxis are age dependent. However, little is known about typical features of anaphylaxis in patients aged 65 years or more. The data from the Network for Online Registration of Anaphylaxis (NORA) considering patients aged ≥65 (elderly) in comparison to data from adults (18-64 years) regarding elicitors, symptoms, comorbidities, and treatment measures were analyzed. We identified 1,123 elderly anaphylactic patients. Insect venoms were the most frequent elicitor in this group ( < 0.001), followed by drugs like analgesics and antibiotics. Food allergens elicited less frequently anaphylaxis ( < 0.001). Skin symptoms occurred less frequently in elderly patients (77%, < 0.001). The clinical symptoms were more severe in the elderly (51% experiencing grade III/IV reactions), in particular when skin symptoms ( < 0.001) were absent. Most strikingly, a loss of consciousness (33%, < 0.001) and preexisting cardiovascular comorbidity (59%, < 0.001) were more prevalent in the elderly. Finally, adrenaline was used in 30% of the elderly (vs. 26% in the comparator group, < 0.001) and hospitalization was more often required (60 vs. 50%, < 0.001). Anaphylaxis in the elderly is often caused by insect venoms and drugs. These patients suffer more often from cardiovascular symptoms, receive more frequently adrenaline and require more often hospitalization. The data indicate that anaphylaxis in the elderly tends to be more frequently life threatening and patients require intensified medical intervention. The data support the need to recognize anaphylaxis in this patient group, which is prone to be at a higher risk for a fatal outcome.
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http://dx.doi.org/10.3389/fimmu.2019.00750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491699PMC
October 2020

Hereditäres Angioödem in Österreich: Prävalenz und regionale Besonderheiten.

J Dtsch Dermatol Ges 2019 04;17(4):416-424

Universitätsklinik für Dermatologie und Venerologie, Medizinische Universität Graz, Österreich.

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http://dx.doi.org/10.1111/ddg.13815_gDOI Listing
April 2019

Hereditary angioedema in Austria: prevalence and regional peculiarities.

J Dtsch Dermatol Ges 2019 Apr 18;17(4):416-423. Epub 2019 Mar 18.

Department of Dermatology and Venereology, Medical University of Graz, Austria.

Background: Data on the prevalence and clinical features of Austrian patients with hereditary angioedema (HAE) with C1-inhibitor (C1-INH) deficiency (HAE-1) or dysfunction (HAE-2) are lacking.

Methods: Current baseline data were collected in a national survey. The records of HAE patients at the Medical University of Graz were analyzed with regard to clinical characteristics.

Results: A total of 137 patients were identified, yielding a prevalence of 1 : 64,396. The median age at the onset of symptoms was 6.5 years, and the median age at the time of correct diagnosis 21.0 years. The median delay in diagnosis was 15.0 years for newly diagnosed patients without a family history of HAE. Patients with a family history of HAE received an immediate diagnosis. HAE patients without a family history of HAE and born before 1960 had to wait a median of 16.0 years until they were diagnosed correctly. Patients born after 1980 still experienced a median diagnostic delay of 6.5 years.

Conclusion: Patients with this condition still face an excessive diagnostic delay in some parts of Austria, or their disorder may even remain unrecognized by specialists. This underlines the need for better awareness of the disease.
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http://dx.doi.org/10.1111/ddg.13815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850089PMC
April 2019

Does clinical outcome of birch pollen immunotherapy relate to induction of blocking antibodies preventing IgE from allergen binding? A pilot study monitoring responses during first year of AIT.

Clin Transl Allergy 2018 8;8:39. Epub 2018 Oct 8.

1Department of Biosciences, University of Salzburg, Hellbrunnerstraße 34, 5020 Salzburg, Austria.

Background: The clinical benefit of allergen-specific immunotherapy (AIT) involves induction of blocking antibodies. It is not clear if these antibodies function via steric hindrance alone or a combination of levels, avidities, and epitope specificities, and clinical outcome cannot be predicted. We aim to in-depth characterize serum antibody profiles during birch pollen AIT, investigate therapy-induced antibodies for their capacity to block IgE binding to Bet v 1 and correlate data with clinical outcomes.

Methods: Immune responses of five birch pollen allergic patients were monitored during the first year of AIT by nasal provocation tests (NPTs), ImmunoCAP, immunoblots, direct and avidity enzyme-linked immunosorbent assays, mediator release assays, facilitated antigen binding (FAB) assays, and inhibition mediator release assays.

Results: There was no correlation between NPT results and therapy-induced changes in levels (IgE, IgG, IgA, IgM), avidities, or mediator release potency of Bet v 1-specific antibodies. In FAB assays, blocking antibodies initiated upon AIT were shown to prevent formation of Bet v 1-IgE complexes of an indicator serum pool and significantly correlated with clinical readout. Inhibition mediator release assays using patient-specific IgE for passive sensitization revealed therapy-induced blocking capacities with very good correlation to NPT results. Notably, this assay was the only one to detect a non-responder during treatment in this pilot study.

Conclusions: Clinical outcome of AIT depends on induction of blocking antibodies able to prevent the patient's own IgE from allergen binding. Monitoring of clinical efficacy seems to be best achieved using the inhibition mediator release assay, as development of relevant blocking antibodies can be verified in a patient-tailored manner.
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http://dx.doi.org/10.1186/s13601-018-0226-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174570PMC
October 2018

Influence of Intrinsic and Lifestyle Factors on the Development of IgE Sensitization.

Int Arch Allergy Immunol 2017 28;173(2):99-104. Epub 2017 Jun 28.

Department of Molecular Biology, University of Salzburg, Salzburg, Austria.

Background: IgE sensitization is a prerequisite for the development of allergic symptoms. The investigation of factors influencing the development of IgE is therefore crucial for understanding the onset of allergic diseases.

Methods: This epidemiological study investigated personal, intrinsic, and lifestyle factors in a nonselected cohort of 501 Austrian adolescents (aged 12-21 years). IgE levels to 112 allergen molecules were analyzed in the serum of participants using the ImmunoCAP ISAC®. Allergic sensitization, IgE levels to single allergens, and ISAC score sums were correlated with results obtained from a questionnaire.

Results: In this adolescent cohort, male participants showed a higher sensitization frequency (56.8%) compared to females (50.9%) and significantly increased IgE levels to profilins. Underweight subjects demonstrated a stronger IgE sensitization. Family size inversely correlated with IgE levels to PR-10 allergens, and predominately paternal allergies were a predictive factor for IgE sensitization in the children. Vaccination, breastfeeding, and delivery mode showed no influence, while a highly protective effect was observed for growing up on a farm. Of all of the investigated lifestyle factors, only smoking significantly influenced the risk for IgE development. Participants with moderate frequencies of colds showed increased sensitization levels.

Conclusion: A hereditary predisposition and lifestyle factors such as a farming environment, smoking, family size, body weight, or frequency of colds significantly influenced the development of allergen-specific IgE in this cohort of adolescents.
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http://dx.doi.org/10.1159/000475499DOI Listing
September 2017

Exposure to Indoor Allergens in Different Residential Settings and Its Influence on IgE Sensitization in a Geographically Confined Austrian Cohort.

PLoS One 2017 3;12(1):e0168686. Epub 2017 Jan 3.

Department of Molecular Biology, University of Salzburg, Salzburg, Austria.

Background: Exposure to indoor allergens is crucial for IgE sensitization and development of allergic symptoms. Residential settings influence the allergen amount in house dust and hence allergic sensitization. Within this study, we investigated allergen exposure and molecule-based IgE levels in a geographically confined region and evaluated the impact of housing, pets and cleaning.

Methods: 501 adolescents from Salzburg, Austria participated in this cross-sectional study. House dust samples were examined regarding major mite, cat, dog, and mold allergens using a multiplex assay. Serum samples of participants were analyzed for specific IgE to Der p 1, Der p 2, Fel d 1, Can f 1 and Alt a 1 using the multiplex array ImmunoCAP ISAC. Information on allergies, living areas, dwelling form (house, flat, farm), pets, and household cleanliness were obtained by a questionnaire.

Results: In investigated house dust samples, the concentration of cat allergen was highest while the prevalence of mold allergens was very low. Participants showed IgE sensitization to Der p 1 (13.2%), Der p 2 (18.2%), Fel d 1 (14.4%), Can f 1 (2.4%) and Alt a 1 (2.0%). In alpine regions, lower mite allergen concentrations were detected which correlated with reduced IgE levels. A trend for increased sensitization prevalence from rural to alpine to urban regions was noted. Living on farms resulted in lower sensitization prevalence to mite and cat allergens, even though exposure to mites was significantly elevated. The presence of cats was associated with a lower sensitization rate and IgE levels to cat and mite allergens, and less frequent allergic diseases. Cleaning did not impact allergen concentrations, while IgE reactivity to mites and allergic diseases were more pronounced when living in cleaner homes.

Conclusion: Allergen exposure to indoor allergens was influenced by setting of homes. Living in a farm environment and having a cat at home showed a protective effect for IgE sensitization and allergies. This cross-sectional study in combination with hereditary and lifestyle factors enables development of risk schemes for a more efficient management and potential prevention of allergic diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168686PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207653PMC
August 2017

Crystal structure of Pla l 1 reveals both structural similarity and allergenic divergence within the Ole e 1-like protein family.

J Allergy Clin Immunol 2017 07 10;140(1):277-280. Epub 2016 Dec 10.

Department of Molecular Biology, University of Salzburg, Salzburg, Austria; Christian Doppler Laboratory for Biosimilar Characterization, University of Salzburg, Salzburg, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2016.10.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695661PMC
July 2017

Tackling Bet v 1 and associated food allergies with a single hybrid protein.

J Allergy Clin Immunol 2017 Aug 7;140(2):525-533.e10. Epub 2016 Dec 7.

Department of Molecular Biology, University of Salzburg, Salzburg, Austria. Electronic address:

Background: Allergy vaccines should be easily applicable, safe, and efficacious. For Bet v 1-mediated birch pollen and associated food allergies, a single wild-type allergen does not provide a complete solution.

Objective: We aimed to combine immunologically relevant epitopes of Bet v 1 and the 2 clinically most important related food allergens from apple and hazelnut to a single hybrid protein, termed MBC4.

Methods: After identification of T cell epitope-containing parts on each of the 3 parental allergens, the hybrid molecule was designed to cover relevant epitopes and evaluated in silico. Thereby a mutation was introduced into the hybrid sequence, which should alter the secondary structure without compromising the immunogenic properties of the molecule.

Results: MBC4 and the parental allergens were purified to homogeneity. Analyses of secondary structure elements revealed substantial changes rendering the hybrid de facto nonreactive with patients' serum IgE. Nevertheless, the protein was monomeric in solution. MBC4 was able to activate T-cell lines from donors with birch pollen allergy and from mice immunized with the parental allergens. Moreover, on immunization of mice and rabbits, MBC4 induced cross-reactive IgG antibodies, which were able to block the binding of human serum IgE.

Conclusion: Directed epitope rearrangements combined with a knowledge-based structural modification resulted in a protein unable to bind IgE from allergic patients. Still, properties to activate specific T cells or induce blocking antibodies were conserved. This suggests that MBC4 is a suitable vaccine candidate for the simultaneous treatment of Bet v 1 and associated food allergies.
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http://dx.doi.org/10.1016/j.jaci.2016.09.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693327PMC
August 2017

Elevated Toll-Like Receptor-Induced CXCL8 Secretion in Human Blood Basophils from Allergic Donors Is Independent of Toll-Like Receptor Expression Levels.

PLoS One 2016 12;11(2):e0149275. Epub 2016 Feb 12.

Department of Molecular Biology, University of Salzburg, Salzburg, Austria.

Human blood basophils have recently gained interest in addition to their function as allergic effector cells. Previous work suggests the involvement of innate immune mechanisms in the development and exacerbation of allergic responses, which might be mediated by basophils. We assayed the expression levels of Toll-like receptor (TLR) 1, 2, 4 and 6 on purified basophils from birch pollen-, house dust mite-, and non-allergic individuals. Additionally, we compared cytokine and chemokine secretion upon TLR stimulation in these basophil donor groups. Expression of TLR4 on the basophils of the allergic donor groups was decreased and CXCL8 secretion was elevated upon stimulation of TLR1/2 and TLR2/6 compared to the non-allergic donors. Decreased TLR expression and elevated CXCL8 secretion may represent possible mechanisms for aggravation of allergic symptoms in case of parasitic infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0149275PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752351PMC
July 2016

Nanoparticle-allergen interactions mediate human allergic responses: protein corona characterization and cellular responses.

Part Fibre Toxicol 2016 Jan 16;13. Epub 2016 Jan 16.

Department of Molecular Biology, Division of Allergy and Immunology, University of Salzburg, Hellbrunnerstr, 34, 5020, Salzburg, Austria.

Background: Engineered nanomaterials (ENMs) interact with different biomolecules as soon as they are in contact, resulting in the formation of a biomolecule 'corona'. Hence, the 'corona' defines the biological identity of the ENMs and could affect the response of the immune system to ENM exposure. With up to 40 % of the world population suffering from type I allergy, a possible modulation of allergen effects by binding to ENMs is highly relevant with respect to work place and consumer safety. Therefore, the aim of this present study was to gain an insight into the interactions of gold nanoparticles with different seasonally and perennially occurring outdoor and indoor allergens.

Methods: Gold nanoparticles (AuNPs) were conjugated with the major allergens of birch pollen (Bet v 1), timothy grass pollen (Phl p 5) and house dust mite (Der p 1). The AuNP-allergen conjugates were characterized by means of TEM negative staining, dynamic light scattering (DLS), z-potential measurements and hyperspectral imaging. Furthermore, 3D models were constructed, based on the characterization data, to visualize the interaction between the allergens and the AuNPs surface. Differences in the activation of human basophil cells derived from birch/grass pollen- and house dust mite-allergic patients in response to free allergen and AuNP-allergen conjugates were determined using the basophil activation assay (BAT). Potential allergen corona replacement during BAT was controlled for using Western blotting. The protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was assessed, by an enzymatic activity assay and a cellular assay pertaining to lung type II alveolar epithelial cell tight junction integrity.

Results: The formation of a stable corona was found for all three allergens used. Our data suggest, that depending on the allergen, different effects are observed after binding to ENMs, including enhanced allergic responses against Der p 1 and also, for some patients, against Bet v 1. Moreover elevated protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was found.

Conclusion: In summary, this study presents that conjugation of allergens to ENMs can modulate the human allergic response, and that protease activity can be increased. Graphical Abstract Cross-linking of IgE receptors and degranulation of human basophils due to epitope alignment of nanoparticle-coated allergens.
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http://dx.doi.org/10.1186/s12989-016-0113-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715273PMC
January 2016

Sensitivity and specificity of Hymenoptera allergen components depend on the diagnostic assay employed.

J Allergy Clin Immunol 2016 05 5;137(5):1603-5. Epub 2016 Jan 5.

Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria; Allergy Outpatient Clinic Reumannplatz, Vienna, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2015.10.041DOI Listing
May 2016

Triggers and treatment of anaphylaxis: an analysis of 4,000 cases from Germany, Austria and Switzerland.

Dtsch Arztebl Int 2014 May;111(21):367-75

Allergy Center Charité, Department of Dermatology, Venerology and Allergology, Charité - Universitätsmedizin Berlin, ADAC Air Rescue Service Senftenberg, Department of Dermatology and Venereology, Medical University of Graz, Austria, Department of Pediatrics, Pneumonology and Immunology, Charité - Universitätsmedizin Berlin, Allergy Clinic, Department of Dermatology, SALK, Paracelsus Medical University, Salzburg, Austria, Pediatric Allergology, University Children's Hospital Zurich, Zurich, Switzerland, Department of Dermatology, University Hospital Erlangen-Nürnberg, Department of Pediatric Pneumology and Allergology at the KID Center, Dresden-Friedrichstadt, Department of Dermatology, Venerology and Allergy at the Saarland University, Homburg/Saar, Department of Allergology, Johanniter-Krankenhaus im Fläming Treuenbrietzen GmbH, Treuenbrietzen, Department of Internal Medicine I: Pneumology & Allergology/Immunology, Friedrich Schiller University Jena, Department of Pediatric Pulmonology and Allergology, Children's Hospital of the University of Cologne, Allergy Unit, Department of Dermatology, University Hospital Basel, Basel, Schweiz, Department of Dermatology, Venereology and Allergology, University of Leipzig, Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Margitta Worm and Oliver Eckermann have equally contributed to the manuscript.

Background: Anaphylaxis is the most severe manifestation of a mast cell-dependent immediate reaction and may be fatal. According to data from the Berlin region, its incidence is 2-3 cases per 100 000 persons per year.

Method: We evaluated data from the anaphylaxis registry of the German-speaking countries for 2006-2013 and data from the protocols of the ADAC air rescue service for 2010-2011 to study the triggers, clinical manifestations, and treatment of anaphylaxis.

Results: The registry contained data on 4141 patients, and the ADAC air rescue protocols concerned 1123 patients. In the registry, the most common triggers for anaphylaxis were insect venom (n = 2074; 50.1%), foods (n = 1039; 25.1%), and drugs (n = 627; 15.1%). Within these groups, the most common triggers were wasp (n = 1460) and bee stings (n = 412), legumes (n = 241), animal proteins (n = 225), and analgesic drugs (n = 277). Food anaphylaxis was most frequently induced by peanuts, cow milk, and hen's egg in children and by wheat and shellfish in adults. An analysis of the medical emergency cases revealed that epinephrine was given for grade 3 or 4 anaphylaxis to 14.5% and 43.9% (respectively) of the patients in the anaphylaxis registry and to 19% and 78% of the patients in the air rescue protocols.

Conclusion: Wasp and bee venom, legumes, animal proteins, and analgesic drugs were the commonest triggers of anaphylaxis. Their relative frequency was age-dependent. Epinephrine was given too rarely, as it is recommended in the guidelines for all cases of grade 2 and above.
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http://dx.doi.org/10.3238/arztebl.2014.0367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075276PMC
May 2014

Plantago lanceolata: an important trigger of summer pollinosis with limited IgE cross-reactivity.

J Allergy Clin Immunol 2014 Aug 1;134(2):472-5. Epub 2014 Apr 1.

Department of Dermatology, Paracelsus Medical University Salzburg, Salzburg, Austria.

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http://dx.doi.org/10.1016/j.jaci.2014.02.016DOI Listing
August 2014

Marker allergens of weed pollen - basic considerations and diagnostic benefits in the clinical routine: Part 16 of the Series Molecular Allergology.

Allergo J Int 2014;23(8):274-280. Epub 2014 Dec 23.

Department of Molecular Biology, University of Salzburg, Salzburg, Austria ; Christian Doppler Laboratory for Biosimilar Characterization, University of Salzburg, Salzburg, Austria ; Christian Doppler Laboratory for Biosimilar Characterization Department of Molecular Biology, University of Salzburg, Hellbrunnerstraße 34, 5020 Salzburg, Austria.

The term weed is referring to plants used as culinary herbs and medicinal plants as well as ecologically adaptive and invasive segetal plants. In Europe, pollen of ragweed, mugwort, English plantain and pellitory are the main elicitors of weed pollen allergies. Presently, 35 weed pollen allergens have been identified. The most relevant belong to the protein families of pectate lyases, defensin-like proteins, non-specific lipid transfer proteins, and Ole e 1-like proteins. The sensitization frequency depends on geographic regions and might affect more than 50 % of pollen allergic patients in distinct regions. Due to overlapping flowering seasons, similar habitats, polysensitizations and cross-reactive (pan)-allergens, it is difficult to diagnose genuine weed pollen sensitization using pollen extracts. Marker allergens for component-resolved diagnostics are available for the important weed pollen. These are Amb a 1 (ragweed), Art v 1 (mugwort), Pla l 1 (English plantain) and Par j 2 (pellitory). Molecule-based approaches can be used to identify the primary sensitizer and thus enable selection of the appropriate weed pollen extracts for allergen immunotherapy.
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http://dx.doi.org/10.1007/s40629-014-0033-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479474PMC
December 2014

Clinical effectiveness of hymenoptera venom immunotherapy: a prospective observational multicenter study of the European academy of allergology and clinical immunology interest group on insect venom hypersensitivity.

PLoS One 2013 20;8(5):e63233. Epub 2013 May 20.

Department of Dermatology and Allergology, Ludwig-Maximilians-Universität, München, Germany.

Background: Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors.

Objective: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase.

Methods: In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models.

Results: 22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate.

Interpretation: It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063233PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659083PMC
December 2013

Implementation of anaphylaxis management guidelines: a register-based study.

PLoS One 2012 10;7(5):e35778. Epub 2012 May 10.

Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medical Centre Berlin, Berlin, Germany.

Background: Anaphylaxis management guidelines recommend the use of intramuscular adrenaline in severe reactions, complemented by antihistamines and corticoids; secondary prevention includes allergen avoidance and provision of self-applicable first aid drugs. Gaps between recommendations and their implementation have been reported, but only in confined settings. Hence, we analysed nation-wide data on the management of anaphylaxis, evaluating the implementation of guidelines.

Methods: Within the anaphylaxis registry, allergy referral centres across Germany, Austria and Switzerland provided data on severe anaphylaxis cases. Based on patient records, details on reaction circumstances, diagnostic workup and treatment were collected via online questionnaire. Report of anaphylaxis through emergency physicians allowed for validation of registry data.

Results: 2114 severe anaphylaxis patients from 58 centres were included. 8% received adrenaline intravenously, 4% intramuscularly; 50% antihistamines, and 51% corticoids. Validation data indicated moderate underreporting of first aid drugs in the Registry. 20% received specific instructions at the time of the reaction; 81% were provided with prophylactic first aid drugs at any time.

Conclusion: There is a distinct discrepancy between current anaphylaxis management guidelines and their implementation. To improve patient care, a revised approach for medical education and training on the management of severe anaphylaxis is warranted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035778PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349675PMC
September 2012

Dendritic cells activated by IFN-γ/STAT1 express IL-31 receptor and release proinflammatory mediators upon IL-31 treatment.

J Immunol 2012 Jun 25;188(11):5319-26. Epub 2012 Apr 25.

Department of Molecular Biology, University of Salzburg, A-5020 Salzburg, Austria.

IL-31 is a T cell-derived cytokine that signals via a heterodimeric receptor composed of IL-31Rα and oncostatin M receptor β. Although several studies have aimed to investigate IL-31-mediated effects, the biological functions of this cytokine are currently not well understood. IL-31 expression correlates with the expression of IL-4 and IL-13 and is associated with atopic dermatitis in humans, indicating that IL-31 is involved in Th2-mediated skin inflammation. Because dendritic cells are the main activators of Th cell responses, we posed the question of whether dendritic cells express the IL-31R complex and govern immune responses triggered by IL-31. In the current study, we report that primary human CD1c(+) as well as monocyte-derived dendritic cells significantly upregulate the IL-31Rα receptor chain upon stimulation with IFN-γ. EMSAs, chromatin immunoprecipitation assays, and small interfering RNA-based silencing assays revealed that STAT1 is the main transcription factor involved in IFN-γ-dependent IL-31Rα expression. Subsequent IL-31 stimulation resulted in a dose-dependent release of proinflammatory mediators, including TNF-α, IL-6, CXCL8, CCL2, CCL5, and CCL22. Because these cytokines are crucially involved in skin inflammation, we hypothesize that IL-31-specific activation of dendritic cells may be part of a positive feedback loop driving the progression of inflammatory skin diseases.
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http://dx.doi.org/10.4049/jimmunol.1101044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766741PMC
June 2012

Basophil activation test for investigation of IgE-mediated mechanisms in drug hypersensitivity.

J Vis Exp 2011 Sep 16(55). Epub 2011 Sep 16.

Department of Molecular Biology, University of Salzburg.

Hypersensitivity reactions against non-steroidal anti-inflammatory drugs (NSAIDs) like propyphenazone (PP) and diclofenac (DF) can manifest as Type I-like allergic reactions (1). In clinical practice, diagnosis of drug hypersensitivity is mainly performed by patient history, as skin testing is not reliable and oral provocation testing bears life-threatening risks for the patient (2). Hence, evidence for an underlying IgE-mediated pathomechanism is hard to obtain. Here, we present an in vitro method based on the use of human basophils derived from drug-hypersensitive patients that mimics the allergic effector reaction in vivo. As basophils of drug-allergic patients carry IgE molecules specific for the culprit drug, they become activated upon IgE receptor crosslinking and release allergic effector molecules. The activation of basophils can be monitored by the determination of the upregulation of CD63 surface expression using flow cytometry (3). In the case of low molecular weight drugs, conjugates are designed to enable IgE receptor crosslinking on basophils. As depicted in Figure 1, two representatives of NSAIDs, PP and DF, are covalently bound to human serum albumin (HSA) via a carboxyl group reacting with the primary amino group of lysine residues. DF carries an intrinsic carboxyl group and, thus, can be used directly (4), whereas a carboxyl group-containing derivative of PP had to be organochemically synthesized prior to the study (1). The coupling degree of the low molecular weight compounds on the protein carrier molecule and their spatial distribution is important to guarantee crosslinking of two IgE receptor molecules. The here described protocol applies high performance-size exclusion chromatography (HPSEC) equipped with a sequential refractive index (RI) and ultra violet (UV) detection system for determination of the coupling degree. As the described methodology may be applied for other drugs, the basophil activation test (BAT) bears the potential to be used for the determination of IgE-mediated mechanisms in drug hypersensitivity. Here, we determine PP hypersensitivity as IgE-mediated and DF hypersensitivity as non-IgE-mediated by BAT.
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http://dx.doi.org/10.3791/3263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230192PMC
September 2011

[Clinical practise guideline of the special interest group in allergy of the ÖGDV - Drug provocation testing in the diagnosis of cutaneous drug reactions].

Wien Klin Wochenschr 2011 Oct 2;123(19-20):585-91. Epub 2011 Sep 2.

Medizinische Universität Graz, Univ.-Klinik für Dermatologie und Venerologie, Graz, Austria.

Nowadays, clinical and evidence based guidelines are considered one of the major efforts to improve patient care in medical practices as well as hospital settings. In the literature, clinical guidelines have been defined as "systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances", which promote both clinically effective standards and cost-effective care. Despite controversial discussion about the clinical impact of guidelines, they may provide workable recommendations that may thus be important for improving the individual patient's care. Adverse drug reactions (drug allergies, drug hypersensitivities) often represent a major hazard for the affected patient, and a definite diagnosis is important for further drug therapies in most cases. In this context, any diagnostic procedure must be preceded by an individual risk-benefit assessment. Drug provocation testing is regarded as the gold standard, but this kind of testing should be performed in accordance with established criteria and, in the vast majority of cases, in a hospital setting. In this paper we present a clinical guideline for drug provocation testing in Austria.
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http://dx.doi.org/10.1007/s00508-011-0037-5DOI Listing
October 2011

Provoking allergens and treatment of anaphylaxis in children and adolescents--data from the anaphylaxis registry of German-speaking countries.

Pediatr Allergy Immunol 2011 Sep 16;22(6):568-74. Epub 2011 Mar 16.

Department of Dermatology and Allergy, University Hospital Charité Berlin, Germany.

Anaphylaxis is the most severe reaction of an IgE-mediated hypersensitivity. Data about affected patients may help to improve our knowledge of anaphylaxis and its medical care. We analysed data from the anaphylaxis registry of German speaking countries with regard to the provoking allergens and treatment modalities of anaphylaxis in children and adolescents. Inclusion criteria were severe systemic allergic reactions with concomitant pulmonary and/or cardiovascular symptoms. The data are collected by a password-controlled online-questionnaire. For this analysis, data of 197 reported anaphylactic reactions from children and adolescents registered between 2006 and 2009 were included. The data show that within the registered cases the most frequently affected organ systems for children and adolescents were the skin (89%) and the respiratory tract (87%) followed by symptoms of the cardiovascular system (47%) and the gastrointestinal tract (43%). The most frequent elicitors were food allergens accounting for 58% of cases, followed by insect venom (24%) and drugs (8%). The most frequent food allergens were peanuts followed by tree nuts and animal related food products. In 18% aggravating factors such as physical exercise were noted by the clinicians. 26% of the analysed patients had experienced more than one reaction. The data regarding the emergency treatment show that antihistamines (87%) and corticosteroids (85%) were often used but that adrenaline was rarely used (22% of the registered cases). Taken together these data show that the analysis of anaphylaxis by registration of affected individuals can provide data about provoking allergens and treatment measures but also suggest the impact of aggravating factors on anaphylactic reactions. The under-represented usage of adrenaline indicates the need of educational measures for patients and their physicians.
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http://dx.doi.org/10.1111/j.1399-3038.2011.01154.xDOI Listing
September 2011

Proteomic profiling of birch (Betula verrucosa) pollen extracts from different origins.

Proteomics 2011 Apr 25;11(8):1486-98. Epub 2011 Feb 25.

Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.

Pollen of the European white birch is a major source of spring pollinosis in Europe. Pollen-allergy diagnosis and treatment by specific immunotherapy commonly rely on extracts of natural origin. To gain insight into the protein content and its variability, we evaluated the profile of allergenic and non-allergenic proteins in extracts of pollen from different origins by MS-based proteomics. Aqueous extracts prepared from commercially available Swedish birch pollen, pollen collected from Austrian trees and a commercial skin prick extract were analyzed by 1-DE, 2-DE, immunoblotting and mass spectrometry, resulting in a complete inventory of extractable, disease-relevant pollen proteins. A main focus of this study was on the isoform distribution of Bet v 1, the major allergen of birch pollen. Using a combination of intact mass determination and peptide sequencing, five isoforms (a, b, d, f and j) were unequivocally identified in Swedish and Austrian birch pollen extracts, while the skin prick extract contained only isoforms a, b and d. Using the same methods as for Bet v 1, divergencies in the sequence of birch profilin (Bet v 2), a plant panallergen, were solved. The molecular characterization of pollen extracts is relevant for standardization and development of new reagents for specific immunotherapy.
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http://dx.doi.org/10.1002/pmic.201000624DOI Listing
April 2011

Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: a randomised, double-blind, placebo-controlled cross-over study.

Wien Klin Wochenschr 2011 Jan 20;123(1-2):15-20. Epub 2010 Dec 20.

Department of Environmental Dermatology and Venereology, Medical University of Graz, Graz, Austria.

Objectives: The term histamine intolerance stands for a range of symptoms involving various effector organs after the consumption of histamine-rich food. Our intention was to objectify and quantify histamine-associated symptoms and to analyse whether oral administration of the histamine-degrading enzyme diamine oxidase (DAO) caused a reduction of symptoms.

Patients And Methods: Four Austrian centres participated. Patients suspected to be histamine intolerant were recruited. The first step consisted in the open oral provocation of these patients with 75 mg of liquid histamine. Patients who developed symptoms were tested in a randomised double blind crossover provocation protocol using histamine-containing and histamine-free tea in combination with DAO capsules or placebo. Main and secondary symptoms (strongest and weaker symptoms based on a ten-point scale) were defined, the grand total of all symptoms of the individual provocation steps was determined and changes in symptoms after administration of DAO were measured.

Results: Thirty nine patients reacted to the open histamine provocation and were enrolled in the blinded part. Here, both the main and secondary symptoms were not reproducible. Subjects reacted sometimes unexpectedly and randomly. Regarding the total symptom scores, the differences between the three treatment groups were statistically significant. The intake of DAO demonstrated a statistically significant reduction of histamine-associated symptoms compared to placebo (P = 0.014).

Conclusions: Oral provocation with 75 mg of liquid histamine failed to reproduce histamine-associated single symptoms in many patients. One may suggest that histamine-intolerant subjects reacted with different organs on different occasions. As a consequence, reproducibility of single symptoms alone may not be appropriate to diagnose histamine-intolerance whereas a global symptom score could be more appropriate. The fact, that the intake of DAO capsules compared to placebo led to a statistically significant reduction of total symptom scores, may indirectly point in the same direction.
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http://dx.doi.org/10.1007/s00508-010-1506-yDOI Listing
January 2011