Publications by authors named "Ulf Darsow"

81 Publications

Gelatin-Containing Vaccines for Varicella, Zoster, Measles, Mumps, and Rubella Induce Basophil Activation in Patients with Alpha-Gal Syndrome.

Int Arch Allergy Immunol 2021 Mar 18:1-7. Epub 2021 Mar 18.

Department of Dermatology and Allergy Biederstein, School of Medicine, Technical University Munich, Munich, Germany.

Background: The alpha-gal syndrome (AGS) describes a new type I allergy entity to the carbohydrate epitope galactose-α-1,3-galactose (alpha-gal), which is mainly found in mammalian food products (e.g., beef, pork, and venison). Apart from meat products, alpha-gal can also be found in products containing gelatin of bovine or porcine origin. Recent case reports pointed to severe anaphylaxis in patients suffering from AGS after vaccination with vaccines containing hydrolyzed gelatin. It was the objective of this study to evaluate if basophil activation tests (BATs) performed with such vaccines were positive in patients with AGS.

Methods: BAT was performed with different dilutions of a gelatin-containing measles, mumps, and rubella (MMR) live vaccine; an attenuated varicella (V) vaccine; an attenuated V-zoster (VZ) vaccine; a MMR live vaccine not containing gelatin (non-gelatin MMR vaccine) in 2 patients with confirmed AGS, 2 patients highly suspicious for AGS, and 2 healthy individuals without any previous medical history for allergies.

Results: All patients showed strongly positive results for all gelatin-containing vaccines (MMR vaccine, V vaccine, and VZ vaccine). Non-gelatin MMR vaccine was negative. The 2 healthy controls did not show any basophil activation.

Conclusions: Gelatin-containing vaccines should be administered with caution or avoided in patients with AGS because of their high potential to activate basophils indicating a risk for anaphylaxis. Also, BAT is a useful additional tool when it comes to screening for potentially high-risk alpha-gal-containing drugs.
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http://dx.doi.org/10.1159/000514263DOI Listing
March 2021

"Idiopathic" anaphylaxis caused by carboxymethylcellulose in ice cream.

J Allergy Clin Immunol Pract 2021 Jan 10;9(1):555-557.e1. Epub 2020 Nov 10.

Department of Dermatology and Allergy Biederstein, School of Medicine, Technical University of Munich, Munich, Germany.

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http://dx.doi.org/10.1016/j.jaip.2020.10.051DOI Listing
January 2021

Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI), Österreichische Gesellschaft für Pneumologie (ÖGP) in co-operation with the German, Austrian, and Swiss ARIA groups, and the European Academy of Allergy and Clinical Immunology (EAACI).

Authors:
Ludger Klimek Oliver Pfaar Margitta Worm Thomas Eiwegger Jan Hagemann Markus Ollert Eva Untersmayr Karin Hoffmann-Sommergruber Alessandra Vultaggio Ioana Agache Sevim Bavbek Apostolos Bossios Ingrid Casper Susan Chan Alexia Chatzipetrou Christian Vogelberg Davide Firinu Paula Kauppi Antonios Kolios Akash Kothari Andrea Matucci Oscar Palomares Zsolt Szépfalusi Wolfgang Pohl Wolfram Hötzenecker Alexander R Rosenkranz Karl-Christian Bergmann Thomas Bieber Roland Buhl Jeroen Buters Ulf Darsow Thomas Keil Jörg Kleine-Tebbe Susanne Lau Marcus Maurer Hans Merk Ralph Mösges Joachim Saloga Petra Staubach Uta Jappe Klaus F Rabe Uta Rabe Claus Vogelmeier Tilo Biedermann Kirsten Jung Wolfgang Schlenter Johannes Ring Adam Chaker Wolfgang Wehrmann Sven Becker Laura Freudelsperger Norbert Mülleneisen Katja Nemat Wolfgang Czech Holger Wrede Randolf Brehler Thomas Fuchs Peter-Valentin Tomazic Werner Aberer Antje-Henriette Fink-Wagner Fritz Horak Stefan Wöhrl Verena Niederberger-Leppin Isabella Pali-Schöll Wolfgang Pohl Regina Roller-Wirnsberger Otto Spranger Rudolf Valenta Mübecell Akdis Paolo M Matricardi François Spertini Nicolai Khaltaev Jean-Pierre Michel Larent Nicod Peter Schmid-Grendelmeier Marco Idzko Eckard Hamelmann Thilo Jakob Thomas Werfel Martin Wagenmann Christian Taube Erika Jensen-Jarolim Stephanie Korn Francois Hentges Jürgen Schwarze Liam O Mahony Edward F Knol Stefano Del Giacco Tomás Chivato Pérez Jean Bousquet Anna Bedbrook Torsten Zuberbier Cezmi Akdis Marek Jutel

Allergol Select 2020 7;4:53-68. Epub 2020 Sep 7.

European Academy of Allergy and Clinical Immunology (EAACI).

Background: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2.

Materials And Methods: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic.

Results: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future.

Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.
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http://dx.doi.org/10.5414/ALX02166EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480069PMC
September 2020

Allergen immunotherapy in the current COVID-19 pandemic: A position paper of AeDA, ARIA, EAACI, DGAKI and GPA: Position paper of the German ARIA Group in cooperation with the Austrian ARIA Group, the Swiss ARIA Group, German Society for Applied Allergology (AEDA), German Society for Allergology and Clinical Immunology (DGAKI), Society for Pediatric Allergology (GPA) in cooperation with AG Clinical Immunology, Allergology and Environmental Medicine of the DGHNO-KHC and the European Academy of Allergy and Clinical Immunology (EAACI).

Allergol Select 2020 28;4:44-52. Epub 2020 May 28.

German ARIA Group.

No abstract available.
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http://dx.doi.org/10.5414/ALX02147EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304289PMC
May 2020

Anwendung von Biologika bei allergischen und Typ-2-entzündlichen Erkrankungen in der aktuellen Covid-19-Pandemie: Positionspapier des Ärzteverbands Deutscher Allergologen (AeDA)A, der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI)B, der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI)D, der Luxemburgischen Gesellschaft für Allergologie und Immunologie (LGAI)E, der Österreichischen Gesellschaft für Pneumologie (ÖGP)F in Kooperation mit der deutschen, österreichischen, und schweizerischen ARIA-GruppeG und der Europäischen Akademie für Allergologie und Klinische Immunologie (EAACI)H.

Allergo J 2020 24;29(4):14-27. Epub 2020 Jun 24.

Zentrum für Rhinologie & Allergologie, An den Quellen 10, 65183 Wiesbaden, Germany.

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http://dx.doi.org/10.1007/s15007-020-2553-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289636PMC
June 2020

Optoacoustic mesoscopy shows potential to increase accuracy of allergy patch testing.

Contact Dermatitis 2020 Sep 19;83(3):206-214. Epub 2020 May 19.

Department of Dermatology and Allergy, Faculty of Medicine, Technical University of Munich, Munich, Germany.

Background: Differentiation between irritant and allergic skin reactions in epicutaneous patch testing is based largely on subjective clinical criteria, with the risk of high intraobserver and interobserver variability. Novel dermatological imaging using optoacoustic mesoscopy allows quantitative three-dimensional assessment of microvascular biomarkers.

Objectives: We investigated the potential of optoacoustic imaging to improve the precision of patch test evaluation.

Methods: Sixty-nine test reactions and 48 healthy skin sections in 52 patients with suspected type IV allergy were examined using raster-scan optoacoustic mesoscopy.

Results: We identified biomarkers from the optoacoustic images. Allergic reactions were associated with higher fragmentation of skin vasculature than irritant reactions (19.5 ± 9.7 vs 14.3 ± 3.7 fragments/100 pixels ; P < .05), as well as lower ratio of low- to high-frequency acoustic signals (1.6 ± 0.5 vs 2.0 ± 0.6, P < .05). Allergic reactions graded "++" showed higher vessel fragmentation than reactions graded "+" (25.4 ± 13.2 vs 17.1 ± 6.5 fragments/100 pixels ; P < .05). A linear model combining the biomarkers fragmentation and frequency ratio could differentiate allergic from irritant test reactions with an area under the receiving operator characteristic curve of 0.80 (95% confidence interval 0.64-0.91), reaching a sensitivity of 81% and specificity of 63%.

Conclusions: Optoacoustic mesoscopy shows potential to help in differentiating between allergic and irritant test reactions based on novel biomarkers that may reflect vasodilation, vessel tortuosity, and edema.
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http://dx.doi.org/10.1111/cod.13563DOI Listing
September 2020

Pollen season is reflected on symptom load for grass and birch pollen-induced allergic rhinitis in different geographic areas-An EAACI Task Force Report.

Allergy 2020 05 1;75(5):1099-1106. Epub 2020 Mar 1.

German Pollen Information Service Foundation, Berlin, Germany.

Background: The effectiveness of allergen immunotherapy (AIT) in seasonal and perennial allergic rhinitis (AR) depends on the definition of pollen exposure intensity or time period. We recently evaluated pollen and symptom data from Germany to examine the new definitions of the European Academy of Allergy and Clinical Immunology (EAACI) on pollen season and peak pollen period start and end. Now, we aim to confirm the feasibility of these definitions to properly mirror symptom loads for grass and birch pollen-induced allergic rhinitis in other European geographical areas such as Austria, Finland and France, and therefore their suitability for AIT and clinical practice support.

Methods: Data from twenty-three pollen monitoring stations from three countries in Europe and for 3 years (2014-2016) were used to investigate the correlation between birch and grass pollen concentrations during the birch and grass pollen season defined via the EAACI criteria, and total nasal symptom and medication scores as reported with the aid of the patient's hay-fever diary (PHD). In addition, we conducted a statistical analysis, together with a graphical investigation, to reveal correlations and dependencies between the studied parameters.

Results: The analysis demonstrated that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to pollen-induced symptom loads reported by PHD users during birch and grass pollen season. A statistically significant correlation (slightly higher for birch) has been found between the Total Nasal Symptom and Medication Score (TNSMS) and the pollen concentration levels. Moreover, the maximum symptom levels occurred mostly within the peak pollen periods (PPP) following the EAACI criteria.

Conclusions: Based on our analyses, we confirm the validity of the EAACI definitions on pollen season for both birch and grass and for a variety of geographical locations for the four European countries (including Germany from a previous publication) analyzed so far. On this basis, the use of the EAACI definitions is supported in future clinical trials on AIT as well as in daily routine for optimal patient care. Further evaluation of the EAACI criteria in other European regions is recommended.
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http://dx.doi.org/10.1111/all.14111DOI Listing
May 2020

Optical features of human skin revealed by optoacoustic mesoscopy in the visible and short-wave infrared regions.

Opt Lett 2019 Sep;44(17):4119-4122

Detailed assessment of skin conditions or the efficacy of skin treatments could greatly benefit from noninvasively assessing the distribution of cutaneous and subcutaneous structures and biomolecules. We considered ultrawideband raster scan optoacoustic mesoscopy with an extended wavelength range from visible to short-wave infrared and observed previously unseen high-resolution images of lipids colocalized with water, melanin, and hemoglobin distribution in human skin. Based on this contrast, the technique resolves subcutaneous fat, the pilosebaceous unit with complete hair strand and bulb, dermal microvasculature, and epidermal structures. We further visualize melanoidins that form via the Maillard reaction in the ultrathin stratum corneum layer, analyze their absorption spectrum, and separate them from the melanin layer. The suggested method may allow novel interrogation of skin conditions, possibly impacting diagnostics and medical and cosmetic treatments.
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http://dx.doi.org/10.1364/OL.44.004119DOI Listing
September 2019

Allergy and sensitization to Hymenoptera venoms in unreferred adults with a high risk of sting exposure.

World Allergy Organ J 2019 28;12(7):100039. Epub 2019 Jun 28.

Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.

Background: Hymenoptera venom sensitization in highly exposed individuals frequently requires risk assessment for future severe sting reactions. In this study, we determined the prevalence of Hymenoptera venom sensitization in individuals who hunt and fish and analyzed possible correlations between the severity of sting reactions and the IgE sensitization profile.

Methods: In this cross-sectional study, paper-based, self-filled questionnaires about previous insect stings and sting reactions were obtained from individuals who hunt and fish in Bavaria, Germany. Blood samples were taken and analyzed for the levels of tryptase, total IgE and IgE to honey bee (i1) and wasp (13) venom, the recombinant allergens rApi m 1, rApi m 2, rApi m 3, rApi m 5, rApi m 10, rVes v 1, rVes v 5, and the CCD marker molecule MUXF3. Odd ratios (ORs) for sensitization and anaphylaxis and Pearson's correlations for the different allergens were calculated.

Results: Of 257 participants, 50.2% showed a sensitization to honey bee venom (i1), and 58.4% showed sensitization to wasp venom (i3). A total of 98.4% of participants claimed to have been stung at least once. Anaphylaxis was reported in 18.7%, and a local sting reaction was reported in 18.3%. The highest sensitization rates were found for whole venom extracts, sensitization to any of the available recombinant allergens exceeded sIgE levels to honeybee venom (i1) in 28.5% and to wasp venom (i3) in 52.9% of participants. Participants with a history of more than 5 stings showed a higher risk for anaphylaxis.

Conclusions: Sensitization to Hymenoptera venom and their recombinant allergens are present in the majority of individuals who hunt and fish. Sensitization to distinct recombinant allergens does not necessarily affect the severity of sting reactions including anaphylaxis. A meticulous medical history of the number of previous stings as well as systemic reactions remains essential.
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http://dx.doi.org/10.1016/j.waojou.2019.100039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610241PMC
June 2019

Drugs of porcine origin-A risk for patients with α-gal syndrome?

J Allergy Clin Immunol Pract 2019 May - Jun;7(5):1687-1690.e3. Epub 2018 Dec 15.

Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2018.12.005DOI Listing
August 2020

Prevalence and treatment of allergies in rural areas of Bavaria, Germany: a cross-sectional study.

World Allergy Organ J 2018 19;11(1):36. Epub 2018 Nov 19.

1Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technical University of Munich, Biedersteiner Str. 29, 80802 Munich, Germany.

Background: There is a high prevalence of allergies in Germany, with approximately 20% of the population having at least one allergy and only about 10% of these being treated adequately. We conducted a cross-sectional study in a rural area of Bavaria (Southern Germany) to evaluate the prevalence of allergies and their treatment, because research regarding this topic is currently limited.

Methods: Data were collected in 10 offices of non-dermatological doctors using a self-filled questionnaire to ask participants about allergies and treatment.

Results: A total of 641 questionnaires were appropriate for analysis. The prevalence of allergies in the Bavarian countryside was higher than that reported for Germany (37.3% vs. 20.0%). Furthermore, almost a third (30.4%) of allergies were not treated at all. The most frequently consulted therapist was found to be a general practitioner.

Conclusions: Based on the study results, there is a need for prevention programs and establishment of treatments for certain allergies to minimize long-term health effects. Moreover, more studies are needed to analyze the prevalence of allergies in farmers who had a higher prevalence of allergies compared to previously reported prevalence in literature reviews.

Trial Registrations: The study was approved by the ethical review committee of the Technical University Munich (
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http://dx.doi.org/10.1186/s40413-018-0218-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6241034PMC
November 2018

Recall urticaria-A new clinical sign in the diagnosis of alpha-gal syndrome.

J Allergy Clin Immunol Pract 2019 Feb 5;7(2):685-686. Epub 2018 Sep 5.

Department of Dermatology and Allergy Biederstein, Technical University of Munich, Munich, Germany.

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http://dx.doi.org/10.1016/j.jaip.2018.08.026DOI Listing
February 2019

Schmerzhafte Bullae und Erosionen nach Gartenarbeit.

J Dtsch Dermatol Ges 2018 Sep;16(9):1159-1161

Klinik und Poliklinik für Dermatologie am Biederstein, München.

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http://dx.doi.org/10.1111/ddg.13634_gDOI Listing
September 2018

The basophil activation test differentiates between patients with alpha-gal syndrome and asymptomatic alpha-gal sensitization.

J Allergy Clin Immunol 2019 01 17;143(1):182-189. Epub 2018 Aug 17.

Department of Dermatology and Allergy Biederstein, Technical University of Munich, Munich, Germany. Electronic address:

Background: Galactose-alpha-1,3-galactose (alpha-gal) syndrome is characterized by the presence of serum specific IgE antibodies to alpha-gal and delayed type I allergic reactions to the carbohydrate alpha-gal after consumption of mammalian (red) meat products and drugs of mammalian origin. Diagnostics currently rely on patient history, skin tests, determination of serum specific IgE antibodies, and oral food or drug challenges.

Objective: We sought to assess the utility of different basophil parameters (basophil reactivity and sensitivity, the ratio of the percentage of CD63 basophils induced by the alpha-gal-containing allergen to the percentage of CD63 basophils after stimulation with anti-FcεRI antibody [%CD63/anti-FcεRI], and area under the dose-response curve [AUC]) as biomarkers for the clinical outcome of patients with alpha-gal syndrome compared with subjects with asymptomatic alpha-gal sensitization.

Methods: In addition to routine diagnostics, a basophil activation test (Flow CAST) with different concentrations of alpha-gal-containing allergens (eg, commercially available alpha-gal-carrying proteins and pork kidney extracts) was performed in 21 patients with alpha-gal syndrome, 12 alpha-gal-sensitized subjects, and 18 control subjects.

Results: Alpha-gal-containing allergens induced strong basophil activation in a dose-dependent manner in patients. Basophil reactivity at distinct allergen concentrations, the %CD63/anti-FcεRI ratio across most allergen concentrations, the AUC of dose-response curves, and basophil allergen threshold sensitivity (CD-sens) with pork kidney extract were significantly higher in patients with alpha-gal syndrome compared with those in sensitized subjects. All parameters were negative in control subjects.

Conclusion: The basophil activation test should be considered as an additional diagnostic test before performing time-consuming and potentially risky oral provocation tests. The %CD63/anti-FcεRI ratio for all allergens and AUCs for pork kidney were the best parameters for distinguishing patients with alpha-gal syndrome from subjects with asymptomatic alpha-gal sensitization.
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http://dx.doi.org/10.1016/j.jaci.2018.06.049DOI Listing
January 2019

Painful blisters and erosions after gardening.

J Dtsch Dermatol Ges 2018 Sep 16;16(9):1159-1161. Epub 2018 Aug 16.

Department of Dermatology, Am Biederstein Medical Center, Munich, Germany.

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http://dx.doi.org/10.1111/ddg.13634DOI Listing
September 2018

Characterization of the honeybee venom proteins C1q-like protein and PVF1 and their allergenic potential.

Toxicon 2018 Aug 26;150:198-206. Epub 2018 May 26.

Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, Ingolstädter Landstraße 1, 85764 Munich, Germany. Electronic address:

Honeybee (Apis mellifera) venom (HBV) represents an ideal model to study the role of particular venom components in allergic reactions in sensitized individuals as well as in the eusociality of Hymenoptera species. The aim of this study was to further characterize the HBV components C1q-like protein (C1q) and PDGF/VEGF-like factor 1 (PVF1). C1q and PVF1 were produced as recombinant proteins in insect cells. Their allergenic properties were examined by determining the level of specific IgE antibodies in the sera of HBV-allergic patients (n = 26) as well as by their capacity to activate patients' basophils (n = 11). Moreover, the transcript heterogeneity of PVF1 was analyzed. It could be demonstrated that at least three PVF1 variants are present in the venom gland, which all result from alternative splicing of one transcript. Additionally, recombinant C1q and PVF1 from Spodoptera frugiperda insect cells exhibited specific IgE reactivity with approximately 38.5% of sera of HBV-allergic patients. Interestingly, both proteins were unable to activate basophils of the patients, questioning their role in the context of clinically relevant sensitization. Recombinant C1q and PVF1 can build the basis for a deeper understanding of the molecular mechanisms of Hymenoptera venoms. Moreover, the conflicting results between IgE sensitization and lack of basophil activation, might in the future contribute to the identification of factors that determine the allergenic potential of proteins.
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http://dx.doi.org/10.1016/j.toxicon.2018.05.017DOI Listing
August 2018

Safety and efficacy of immunotherapy with the recombinant B-cell epitope-based grass pollen vaccine BM32.

J Allergy Clin Immunol 2018 08 17;142(2):497-509.e9. Epub 2018 Jan 17.

Division of Immunopathology, Department of Pathophysiology and Allergy Research, Medical University Vienna, Vienna, Austria; NRC Institute of Immunology FMBA of Russia, Moscow. Electronic address:

Background: BM32 is a grass pollen allergy vaccine based on recombinant fusion proteins consisting of nonallergenic peptides from the IgE-binding sites of the 4 major grass pollen allergens and the hepatitis B preS protein.

Objective: We sought to study the safety and clinical efficacy of immunotherapy (allergen immunotherapy) with BM32 in patients with grass pollen-induced rhinitis and controlled asthma.

Methods: A double-blind, placebo-controlled, multicenter allergen immunotherapy field study was conducted for 2 grass pollen seasons. After a baseline season, subjects (n = 181) were randomized and received 3 preseasonal injections of either placebo (n = 58) or a low dose (80 μg, n = 60) or high dose (160 μg, n = 63) of BM32 in year 1, respectively, followed by a booster injection in autumn. In the second year, all actively treated subjects received 3 preseasonal injections of the BM32 low dose, and placebo-treated subjects continued with placebo. Clinical efficacy was assessed by using combined symptom medication scores, visual analog scales, Rhinoconjunctivitis Quality of Life Questionnaires, and asthma symptom scores. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology. Allergen-specific antibodies were determined by using ELISA, ImmunoCAP, and ImmunoCAP ISAC.

Results: Although statistical significance regarding the primary end point was not reached, BM32-treated subjects, when compared with placebo-treated subjects, showed an improvement regarding symptom medication, visual analog scale, Rhinoconjunctivitis Quality of Life Questionnaire, and asthma symptom scores in both treatment years. This was accompanied by an induction of allergen-specific IgG without induction of allergen-specific IgE and a reduction in the seasonally induced increase in allergen-specific IgE levels in year 2. In the first year, more grade 2 reactions were observed in the active (n = 6) versus placebo (n = 1) groups, whereas there was almost no difference in the second year.

Conclusions: Injections of BM32 induced allergen-specific IgG, improved clinical symptoms of seasonal grass pollen allergy, and were well tolerated.
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http://dx.doi.org/10.1016/j.jaci.2017.09.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392176PMC
August 2018

The high molecular weight dipeptidyl peptidase IV Pol d 3 is a major allergen of Polistes dominula venom.

Sci Rep 2018 01 22;8(1):1318. Epub 2018 Jan 22.

Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, Member of the German Center of Lung Research (DZL), Munich, Germany.

Hymenoptera venom allergy can cause severe anaphylaxis in untreated patients. Polistes dominula is an important elicitor of venom allergy in Southern Europe as well as in the United States. Due to its increased spreading to more moderate climate zones, Polistes venom allergy is likely to gain importance also in these areas. So far, only few allergens of Polistes dominula venom were identified as basis for component-resolved diagnostics. Therefore, this study aimed to broaden the available panel of important Polistes venom allergens. The 100 kDa allergen Pol d 3 was identified by mass spectrometry and found to be a dipeptidyl peptidase IV. Recombinantly produced Pol d 3 exhibited sIgE-reactivity with approximately 66% of Polistes venom-sensitized patients. Moreover, its clinical relevance was supported by the potent activation of basophils from allergic patients. Cross-reactivity with the dipeptidyl peptidases IV from honeybee and yellow jacket venom suggests the presence of exclusive as well as conserved IgE epitopes. The obtained data suggest a pivotal role of Pol d 3 as sensitizing component of Polistes venom, thus supporting its status as a major allergen of clinical relevance. Therefore, Pol d 3 might become a key element for proper diagnosis of Polistes venom allergy.
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http://dx.doi.org/10.1038/s41598-018-19666-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778000PMC
January 2018

White-fruited strawberry genotypes are not per se hypoallergenic.

Food Res Int 2017 10 4;100(Pt 1):748-756. Epub 2017 Aug 4.

Biotechnology of Natural Products, Technische Universität München, Liesel-Beckmann-Str. 1, 85354 Freising, Germany. Electronic address:

The strawberry fruit Fra a 1-proteins are homologues of the major birch pollen allergen Bet v 1 and have essential biological functions in pigment formation during fruit ripening. Patients affected by allergy against birch pollen tolerated fruits of a naturally occurring white-fruited F.×ananassa genotype, which showed reduced levels of Fra a 1 proteins along with enzymes of the anthocyanin pigment pathway. We evaluated the cross-reactive allergenic potential of a number of naturally occurring white- and red-fruited strawberry varieties to detect genotypes with low allergenic reactivity, whose fruit might be tolerated by patients with mild allergy. Protein extracts of 51 different strawberry varieties (Fragaria×ananassa, F. vesca, and F. nilgerensis) were screened by Western blot analysis with a polyclonal Fra a 1.02 antibody. Besides, activation of basophils of eight atopic patients allergic to birch pollen were studied using Bet v 1a and different concentrations of 15 selected strawberry protein extracts out of the 51 strawberry genotypes. Median percentages of activated basophils stimulated by extracts from white- and red-fruited genotypes ranged from 36 to 84% and 44 to 76%, respectively indicating that white-fruited strawberry are not per se hypoallergenic. Protein extracts from white-fruited F. vesca cv. Yellow Wonder showed the lowest cross-reactivity but high biological variability. The knowledge about the allergenic potential of different strawberry genotypes may help to improve food safety and can serve as starting point for the development of red-fruited hypoallergenic strawberry cultivars.
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http://dx.doi.org/10.1016/j.foodres.2017.07.076DOI Listing
October 2017

Insektenstichreaktion.

MMW Fortschr Med 2017 Jun;159(12):50

, München, Deutschland.

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http://dx.doi.org/10.1007/s15006-017-9849-1DOI Listing
June 2017

Rare Ingestive Food Allergy to Mushroom Boletus badius.

Acta Derm Venereol 2017 Oct;97(9):1134-1135

Department of Dermatology and Allergology, Technical University Munich, DE-80802 Munich, Germany.

is missing (Short communication).
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http://dx.doi.org/10.2340/00015555-2721DOI Listing
October 2017

Utility of basophil activation testing to assess perioperative anaphylactic reactions in real-world practice.

Immun Inflamm Dis 2017 12 5;5(4):416-420. Epub 2017 Jun 5.

Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.

Introduction: Perioperative anaphylactic reactions due to drugs and substances associated with general anesthesia can potentially be life-threatening. The objective of this study was to investigate the significance of the basophil activation test (BAT) for allergy diagnosis work up.

Methods: A total of 14 patients (5 men, 9 women; mean age: 57.8 years) with clinical records of anaphylactic reactions under general anesthesia were studied by means of anesthesia records, skin and serological tests. Eleven healthy subjects without any history of allergic sensitization to anaesthetic drugs served as controls. BATs based on stimulation of whole blood cells measuring CD63 activation of basophils and using CCR3 as basophil marker by flow cytometry (Flow CAST®, BÜHLMANN Laboratories AG, Schönenbuch, Switzerland) were performed with the following substances (in dependence on the history and the skin tests of the patient): analgesics (acetylsalicylic acid, celecoxib, diclofenac, ibuprofen, indometacin, metamizole, paracetamol, propyphenazone, tramadol), antibiotics (PPL (benzylpenicilloyl polylysine), MDM (minor determinant mixture), amoxicillin, cefuroxime, ciprofloxacin, doxycycline, erythromycin, roxithromycin, sulfamethoxazole, trimethoprim), local anesthetics (articaine, bupivacaine, lidocaine, prilocaine, procaine, methyl-4-hydroxybenzoate), narcotics and NMBA (atracurium, cisatracurium, etomidate, neostigmine, midazolam, mivacurium, pancuronium, propofol, pyridostigmine, succinylcholine, sufentanil, thiopental, vecuronium), and other individual substances.

Results: Three patients showed positive results in the BAT: One to metamizole, one to PPL, and one to pancuronium. BATs with these substances were negative in controls.

Conclusions: The BAT should be used complementary to skin tests, especially if IgE-mediated mechanisms are presumed and skin tests are inconclusive. A positive reaction in BAT identifies the culprit agent with high probability.
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http://dx.doi.org/10.1002/iid3.175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5691303PMC
December 2017

Component-resolved evaluation of the content of major allergens in therapeutic extracts for specific immunotherapy of honeybee venom allergy.

Hum Vaccin Immunother 2017 10 11;13(10):2482-2489. Epub 2017 May 11.

a Center of Allergy and Environment (ZAUM) , Technical University of Munich and Helmholtz Center Munich, Member of the German Center of Lung Research (DZL) , Munich , Germany.

Allergen-specific immunotherapy is the only curative treatment of honeybee venom (HBV) allergy, which is able to protect against further anaphylactic sting reactions. Recent analyses on a molecular level have demonstrated that HBV represents a complex allergen source that contains more relevant major allergens than formerly anticipated. Moreover, allergic patients show very diverse sensitization profiles with the different allergens. HBV-specific immunotherapy is conducted with HBV extracts which are derived from pure venom. The allergen content of these therapeutic extracts might differ due to natural variations of the source material or different down-stream processing strategies of the manufacturers. Since variations of the allergen content of therapeutic HBV extracts might be associated with therapeutic failure, we adressed the component-resolved allergen composition of different therapeutic grade HBV extracts which are approved for immunotherapy in numerous countries. The extracts were analyzed for their content of the major allergens Api m 1, Api m 2, Api m 3, Api m 5 and Api m 10. Using allergen-specific antibodies we were able to demonstrate the underrepresentation of relevant major allergens such as Api m 3, Api m 5 and Api m 10 in particular therapeutic extracts. Taken together, standardization of therapeutic extracts by determination of the total allergenic potency might imply the intrinsic pitfall of losing information about particular major allergens. Moreover, the variable allergen composition of different therapeutic HBV extracts might have an impact on therapy outcome and the clinical management of HBV-allergic patients with specific IgE to particular allergens.
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http://dx.doi.org/10.1080/21645515.2017.1323603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647995PMC
October 2017

Fra a 1.02 Is the Most Potent Isoform of the Bet v 1-like Allergen in Strawberry Fruit.

J Agric Food Chem 2016 May 26;64(18):3688-96. Epub 2016 Apr 26.

Biotechnology of Natural Products, Technische Universität München , Freising, Germany.

The strawberry fruit proteins Fra a 1.01E-1.08 are homologues of the major birch pollen allergen Bet v 1. Three of the proteins are known to have essential biological functions in pigment formation during fruit ripening and seem to be responsible for allergic reactions to strawberry fruit. We evaluated the cross-reactive allergenic potential of these putative strawberry allergens in patients allergic to birch pollen. Activation of basophils of eight atopic patients was studied using different concentrations of Fra a 1 isoforms. Bet v 1a was used as control and as atopic patient selection criterion. Although Fra a 1.01E-1.08 have amino acid sequence identities of 74.5-97.5% with Fra a 1.02, the basophil activation mediated by the eight Fra a 1 proteins differed substantially. Fra a 1.03 and Fra a 1.02 showed the highest activation of basophils, 73 and 66% of total basophils, respectively. On the basis of the high relative expression of the gene Fra a 1.02 in ripe strawberry fruits of allergenic varieties, Fra a 1.02 was identified as the main strawberry allergen of the Bet v 1 superfamily. Knowledge of the allergenic potential of Fra a 1.02/1.03 will help to improve food safety and can serve as a valuable marker for the development of red-fruited hypoallergenic strawberry cultivars.
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http://dx.doi.org/10.1021/acs.jafc.6b00488DOI Listing
May 2016

Contact sensitization in prurigo patients.

Contact Dermatitis 2016 Sep 7;75(3):173-9. Epub 2016 Apr 7.

Information Network of Departments of Dermatology (IVDK), University of Göttingen, 37075, Göttingen, Germany.

Background: There are no studies on contact allergy in patients with prurigo. With itch being important in the pathophysiology of prurigo diseases and being a symptom of allergic contact dermatitis, we aimed to investigate contact allergy in patients suffering from prurigo.

Objectives: Exploratory analysis of patch test results in prurigo patients.

Materials And Methods: A retrospective analysis of data of the Information Network of Departments of Dermatology, 2005-2014, was performed.

Results: Of 116 744 patch tested patients, 639 (0.55%) were diagnosed with prurigo. The median age was 61 years, 286 (45%) were pensioners, and 252 (39.5%) had generalized prurigo. The indication for patch testing was exclusion of contact allergy in 412 patients (64.5%), and 223 patients (35%) had at least one positive patch test reaction. There was no distinctive pattern of sensitization. Prurigo patients had significantly more (and stronger) reactions to the irritant control patch test with sodium lauryl sulfate than a control group (27.6% versus 21.0%).

Conclusions: Although prurigo is not a typical clinical manifestation of contact sensitization, our results indicate that patch testing in these patients may be helpful.
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http://dx.doi.org/10.1111/cod.12564DOI Listing
September 2016

α-Gal-a new clue for anaphylaxis in mastocytosis.

J Allergy Clin Immunol Pract 2016 May-Jun;4(3):531-2. Epub 2016 Jan 12.

Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.

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http://dx.doi.org/10.1016/j.jaip.2015.11.027DOI Listing
July 2018

Comparison of molecular and extract-based allergy diagnostics with multiplex and singleplex analysis.

Allergo J Int 2015;24:46-53. Epub 2015 Mar 14.

University Freiburg Medical Center, Department of Exercise Medicine and Sport, University of Freiburg, Freiburg, Germany ; Department of Pneumology, University of Freiburg, Freiburg, Germany ; Department of Pneumology, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany.

Background: ImmunoCAP ISAC 112, is a commercially available molecular allergy IgE multiplex test. Data on the comparison of this rather novel test with extract-based as well as molecular ImmunoCAP singleplex IgE tests is missing.

Objective: To perform a comparison between the ISAC multiplex IgE assay and the ImmunoCAP singleplex test results.

Methods: Serum samples of 101 adults with grass pollen allergy were analysed for sIgE to 112 allergenic molecules represented on the ISAC test as well as to common atopy-related extract-based allergy tests with the ImmunoCAP System (house dust mite [d1], cat [e1], dog [e5], cow's milk [f2], hen's egg [f1], hazelnut [f17], celery [f85], [m6], as well as pollen from birch [t3], hazel [t4], mugwort [w6], and ragweed [w1]). Subsequently statistical analysis was performed with the Spearman rank correlation test and the Clopper-Pearson method in order to compare the ISAC multiplex results with the sIgE singleplex results.

Results: The positive percent agreements (PPA) and negative percent agreement (NPA) of corresponding allergens between the ISAC sIgE test and the extract-based singleplex ImmunoCAP results at cutoff 0.1 kUA/l varied between 60-100 % for PPA and 78-97 % for NPA.

Conclusion: When taking into account corresponding allergens molecular testing with the ISAC multiplex test correlates well with ImmunoCAP singleplex results.
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http://dx.doi.org/10.1007/s40629-015-0046-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686215PMC
March 2015

Identification of cross-reactivity between buckwheat and coconut.

Ann Allergy Asthma Immunol 2015 Dec 9;115(6):530-2. Epub 2015 Oct 9.

Respiratory Medicine and Allergology, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2015.09.008DOI Listing
December 2015

EAACI position paper for practical patch testing in allergic contact dermatitis in children.

Pediatr Allergy Immunol 2015 Nov;26(7):598-606

Department of Dermatology, Dermicis Skin Hospital, Alkmaar, Foundation Pediatric Dermatology, Rotterdam, The Netherlands.

Introduction: Allergic contact dermatitis (ACD) in children appears to be on the increase, and contact sensitization may already begin in infancy. The diagnosis of contact dermatitis requires a careful evaluation of a patient's clinical history, physical examination, and skin testing. Patch testing is the gold standard diagnostic test.

Methods: Based on consensus, the EAACI Task Force on Allergic Contact Dermatitis in Children produced this document to provide details on clinical aspects, the standardization of patch test methodology, and suggestions for future research in the field.

Results: We provide a baseline list of test allergens to be tested in children with suspected ACD. Additional tests should be performed only on specific indications.
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http://dx.doi.org/10.1111/pai.12463DOI Listing
November 2015